Hello, and welcome to DNB Carnegie. My name is Maria Carlsson-Osipova, and I'm a healthcare analyst here at the bank. Today with me in studio, I have Ulf Hannelius, CEO of Diamyd Medical, and we also have Dr. Joshua Vieth, a Senior Director of Research at Breakthrough T1D, and Mark Atkinson, board member of Diamyd Medical, a PhD and professor of diabetes research at the University of Florida. As you can guess, we're going to talk about Diamyd Medical and the interim results that you have posted on Friday and also an add-on on Sunday. Could you just briefly walk us through what you've posted and what were the results, Ulf? Yes. We first announced late Friday evening, Sweden time, the high level of the interim readout. This was a pre-specified interim readout in the ongoing phase III trial with our retogatein investigational therapy. The interim readout in this case, very surprisingly, and we will go into that, showed not only that it wasn't statistically significant, but it actually showed futility, meaning that it was below the threshold of what's considered a futile trial, meaning that given the interim data that was from 174 patients followed for 50 months, given those data, there's a very low likelihood that the full readout coming summer of 2027 with all 321 patients would be positive. This is obviously very surprising that we can go into, like, all the previous data and findings from this. That's what we announced Friday evening, and we have an update on Sunday evening with a bit more details where we also talked a bit about the results when we have looked at the results very high level, which very surprisingly again show basically no effect at all in the full population or in any pre-specified subgroup, which is completely not aligned with any of the previous findings from previous trials or analysis. That's what we have told so far, and what is now ongoing and has been ongoing during the weekend is to really try to find out the reason behind these findings, and we are doing it in different steps now. That's, like, briefly what we have announced. Thank you. Before we jump in and try to dig in the data and try to ask you questions like what could have went wrong, I'd like to maybe ask Dr. Vieth and Mark Atkinson actually about how DIAGNODE-3 came to be, because there was a lot of data that has been gathered from before that you've mentioned, and what have been your roles with Diamyd Medical in the past? Mark, if you want to start, we start with you maybe. Oh, sure. Yes. Going to go with Josh, but I'll be happy to take that. In the mid-1970s, if you wanna go way back, people found that persons had a disorder that we now call type 1 diabetes, and it's different from a disease that we now call type 2 diabetes. Type 1 diabetes is a disease where for reasons that are still unknown, the body mounts an immune response against the insulin-producing cells in the pancreas. Over time, months to years to even decades, a number of beta cells will be destroyed, and then the person becomes dependent on insulin for the rest of their life. Long-term on insulin, it keeps a patient alive, but in reality it's hard to manage their diabetes, so they suffer from eye disorders, heart disease, kidney problems, and foot problems. What happened though in the 1970s was people found out that type 1 is an autoimmune disease, and the way they found that was through the development of tests where they found autoantibodies. About 10 years after that initial finding, it came out that one of the major autoantibodies in type 1 diabetes was GAD. In the early 90s, our CEO formed a company, and since that time has been working through clinical trials, very carefully performed, well designed, international in scope, of quality to try and identify a drug that would either prevent the development of diabetes or provide benefit from the loss of C-peptide, which we can go into later, in those with recent onset disease. Many aspects of the and years of history that led to the formation of this phase III trial. Dr. Vieth, do you have anything to add on to that? Most certainly. You know, our role at Breakthrough T1D is to fund research that leads to therapy and cures for those living with or at risk of type 1 diabetes. A main pillar of our research program is disease-modifying therapies, those that aim to rebalance the immune system, as Mark talked about type 1 diabetes being an autoimmune disease, and to support and preserve somebody's own beta cells. To that regard, we became involved not only in the past research with Diamyd, but with this current phase III trial as a really first-in-class precision approach toward modifying the course of disease in those living with type 1 diabetes. Between you three now on this call, there's an immense experience, decades of experience in diabetes, and you have all mentioned that these are very surprising results. I would like to jump back into the press releases. The biggest question is, what went wrong? Could it be data handling? What are the potential scenarios that you see in front of you? Obviously, there are many potential scenarios. I think as a company, we should refrain from speculating too much. We need to sort of do this work in a very systematic stepwise approach, but also it should go as swiftly as possible without cutting any corners. I mean, first thing to do is obviously make sure that the analysis had been done in the correct way with the correct data. I mean, that's the first initial part to do. After that, considering that all of that is done, then you dig deeper, look into the data to see that, like, has the treatment worked as expected from an immunological perspective, for example, functional perspective, looking at, like, the protocol and treatments, like doing a lot of different tests from all different kinds of angles to really try to do a root cause analysis because I think that's the most important thing right now. I mean, before we can take clear next steps, we need to understand these data. Are they true? If they are true, why do they show basically a complete lack of efficacy when previous trials and data analysis have shown clear trends or significant effects specifically in these genetics, like, subgroup that we are treating now. That's really key at this moment for us as a company, and I think for a wider field as well. You have mentioned in the press releases that the DIAGNODE-3 is going on as is until you have more information. How should we interpret the fact that continuation criteria were not met? Is it, will it be eventually then stopped? How long time will it take? Paused or how are you thinking? Yeah. Well, right now, obviously, we need to always keep the patient safety the most important thing always. Right now, I mean, we need to make sure we do these first steps of the analysis. That should be relatively quick to just understand were the analysis done in the right way with the right data. If in case that would happen that's not the case, we need to redo the analysis with the right data. In that case, we don't want to have already stopped the trial and sort of basically destroyed the whole value of the trial by doing that. We need to take that in steps. The next step could be then if we see that, well, these data are true, obviously, there's an obvious step then. The trial should be discontinued and unblind all the data to really get access to everything, to understand the data we have then in detail. We should be careful not to unblind ourselves too early because that really compromises the integrity of the trial, and it can be very difficult to save the trial after that has been done. There's a big value, obviously, in looking at the data, but it can't be used from a, let's say, registrational purpose at that point. You mentioned not to unblind the data, but have you seen some data now, and have you seen any difference across subgroups? There's a question here in the chat that goes as, "Is it no difference as in zero increase of C-peptide compared to placebo even for super responders? Yeah. Again, in the press release, we mentioned, obviously, it's very high level, but we said that we don't see any observable effect anywhere, including in pre-specified subgroups, which also includes the potential super responder group. Again, these findings are what makes this especially surprising given all the previous data and experience. Mark and Dr. Vieth, do you have anything to add here? What were your initial reactions when you got the data? Shock. It's been three days of that or since Friday night that came through because again, just to emphasize a point that Ulf made earlier, this was a first-in-class precision-based medicine, meaning I mentioned earlier on that we've been identifying these autoantigens, these self components of beta cells. People have tried to use them and the results have been mixed. Diamyd came with a unique approach of essentially identifying individuals with the highest probability of responding. In its study design, we refer to it as precision medicine-based, which only adds to the shock in terms of seeing the results, and this will certainly be looked at as why this trial didn't verify what the other ones did. There's one other point I wanna make is sometimes phase III trials are paused or issues are raised around safety and I wanna make sure to everybody who's either an investor or a patient in the trial, this is not an issue of safety that we're talking about here. Diamyd has been administered to, you know, upwards of 1,000 individuals with safety concerns that never precluded it from being used in a trial. So this is not like some trials where there's questions around safety. This is a very safe drug. Josh? Well, certainly, you know, first and foremost, Breakthrough T1D is a patient advocacy organization, and we share the shock with the results and are as surprised as both Mark and the Diamyd team are. You know, what really stands out here is the inconsistency with prior data. Obviously, for those that are living with or at risk of type 1 diabetes, this is an understandably disappointing result. But in particular at Breakthrough T1D, we don't look at trials in isolation. We work toward building sort of a cumulative understanding across studies. If we take these current results into context, from our perspective, the most important next step is really rigorous analysis of the data before considering the next strategic move forward. Thank you. Are there any alternative development pathways for [audio distortion]? Well, it's quite specific for autoimmune type 1 diabetes. Mm-hmm. Obviously, this is what the phase III is in what's called Stage 3, basically newly diagnosed, clinically diagnosed patients with type 1 diabetes and specifically with this genetic profile. We have some data and experience in a small trial ongoing in Sweden in what's called Stage 1 and Stage 2. These are individuals then that have a very high risk of getting clinically diagnosed eventually with the disease. They already have an autoimmune disease ongoing, but they have no symptoms of the disease. Basically feel like healthy individuals. There you go then early on to treat in a more preventive fashion to delay, in the best case, like, make sure that they never go as far as clinical diagnosis. That could be one future step, obviously, given that we already have some experience from there with the convenience and safety of the drug. Very critical that we first understand these results before we take any decisions in moving forward regarding that. There could be, I know this has been public information. In theory, there could be some other applications in these more neurological disorders where patients have GAD autoantibodies as well, like autoimmune neurological disorders. Again, that's only on a, I would say, still on a theoretical basis. There's some non-clinical potential evidence around that one. But I would say that it's quite limited to this since the protein is very specific for autoimmune type 1 diabetes and some of these very rare neurological disorders. There are some questions that echo the same, basically the same idea. What additional information can we expect from you in updates over the coming period? People are asking here, what information can we expect on a weekly basis, in a month. Yeah. On a short-term basis. Yeah, of course. I can't promise anything. What I can promise is that we'll try to be as transparent and communicative as possible in these times. The first step now in the analysis is really to make sure that the analysis has been done in the correct manner with the right data, and that obviously we will, once we have certainty around that part, we'll communicate. Then depending on that outcome, we go into the next steps and try again to be as transparent as possible. We also need to be careful in, especially as a public company now, when you communicate, you need to give enough and correct information, not to give, like, only parts of information that might change later on and we create more confusion in the market than we should. We will definitely aspire to be as transparent as possible and try to do this analysis as swift as possible, but again, not do any rash decisions or decisions we come to regret later on. Mm-hmm. This is my- Can I just say. Yes, please, Mark. I should say that was a well-put answer by Ulf. One thing to make sure is that it's not just one individual or a handful of individuals that's gonna be taking a look at this. Every potential source of this outcome will be looked at. Diamyd has a very active external scientific advisory board with people from the United States, from Sweden, from the United Kingdom. They'll all be looking into this and asking what medically, scientifically could have contributed to this. The management team at Diamyd will be poring through this data, working with the CRO to try and identify and again make sure that there were no sources of error in terms of this. We have the production facility in Umeå that I'm sure will be contributing to look at the source material, making sure that there were no issues there. You have the board of directors that will work together with funders and take special effort to make sure that the investors in the company, that their rights and interests both in the past and moving forward continue and in a most professional way. Thank you, Mark. There's a question here which is mostly directed to you, Ulf. It's about the cash position. How long do you expect the cash to last? The share issue that has been announced last week, does it have any conditions that could prevent it from going through, or has it already gone through? Our cash, I mean, we very recently published our quarterly report. In U.S. dollars, it's around $20 million. We recently conducted this equity investment of $25 million, and that has gone through. The current cash position is around $40 million, something like this, or in Swedish, SEK 400 million. With current activities, well, obviously these current activities can change quite significantly depending now on next steps and the analysis ongoing. With the current burn rate, we have a run rate of around 18-24 months, so that's quite considerable. Obviously, now the most important thing is that we use our cash position and everything we are doing in the best possible way. I mean, it sounds maybe. I wouldn't say naive, but maybe offensive even to say that we obviously need to maximize shareholder value here. That's also why it's so critical now that the next steps that we are doing, that we do the right next steps. Don't rush into anything, but we can't let things take forever as well, given this. I mean, it was a share. I mean, no conditions apply to that one. A lot of questions here in the chat now are incoming about. I think people just want to discuss scientific rationale and some ideas. One of those questions is, how large were samples of previous analysis for specific subgroups? Could it be an unlucky case of honeymoon effect during all previous studies? I mean, you never know. I mean, we hopefully will come to the root cause of this. I mean, thinking about previous trials and if we specifically think about this genetic subgroup, which is roughly half of all the patients we have previously treated. So let's say we've done some meta-analysis with more than 600 individuals, so around 300 of those had the right genetic profile, and you can see a clearly statistically significant treatment effect in those. And we have also when you look at the single trial basis, for example, the original phase II that was run in Sweden, and the phase III that was run in Europe and a TrialNet phase II in the U.S. You see in this genetic subgroup that there's a very clear treatment effect. Now we had 174 patients with the right genetic profile treated for 15 months or followed up for 15 months, and we see nothing. That's in stark contrast to all these previous trials and data that I mentioned. That it would be a honeymoon effect, I mean, you never know. I mean, you can have like this freak luck that it just happened this time or even lower likelihood that all the previous trials were just random findings. I mean, we need to really get to the bottom of this before we can answer these questions. Another question which is a little bit on the same topic of, like thinking about, okay, what is the rationale and the history? Could it be that anti-GAD response is not enough to cover the autoimmune repertoire that may be in play with Stage 3 patients, given the diversity of known islet autoantigens? That could definitely be. I mean, again, the hypothesis that we are aiming at here is to, with individuals with this specific genetic profile, the DR3-DQ2 HLA haplotype, it's known that that associates with GAD autoantibody first disease. We treat with GAD, so they potentially have a GAD-driven autoimmune disease. There will be epitope spreading, meaning that the ones who are clinically diagnosed usually have multiple autoantibodies against different ones. Maybe in this case, GAD was the initiating, sort of what initiated that autoimmune attack, and maybe that's then the driver behind that individual's disease. If you would add additional autoantigens into the mix, potentially it could work even better. That's why we also have like patterns around using insulin as an antigen for the other big HLA subgroup and maybe a combination of both antigens for those who are heterozygous, who have both. Again, given these results, we really need to investigate this data to understand what happened, if there's anything that went wrong, or is this the truth, to revisit that hypothesis. Again, these data don't they don't mean that all the previous data aren't true, but we need to understand this current case now before we can answer more. Maybe Josh and Mark, regarding, I mean, immunology is obviously a difficult area, and there are different answers always depending on who you ask, but it's a valid question. I want to have Josh and Mark to- Would you like to chime in? Go ahead, Josh. Yeah. I think what this result reinforces is that immune interventions in type 1 diabetes are complex and highly context and perhaps even stage dependent. I think rather than casting out broadly on a precision approach in general, this just really highlights the importance of understanding the mechanism, the timing of intervention, and the stage of intervention more precisely. Right. Now all I'll add is that I hope that this is just what we'll look back on one day as a very short-term disappointment for what will eventually be a long-term benefit for patients with type 1 diabetes or those that are going to risk the disease. One of the key things that Diamyd has going for it, and again, Josh had mentioned, Breakthrough T1D's emphasis on disease-modifying therapies, is that many news reports go out talking about various other forms of therapies that have the ability to either restore insulin production or retain it. The vast majority of those therapies involve something now we refer to as immunosuppression. Now even those are getting better, but there's been long-held concerns about using immunosuppressive drugs. Not all of them are, but this one would avoid all of this, the Diamyd that I'm speaking of, through its antigen specificity. We cannot, as a community that cares about those with diabetes, give up on antigen-specific therapies. It's turning out, as Joshua said earlier, a difficult field, but one day I'm confident we'll figure it out one day. Thank you, Mark. Thank you, Dr. Vieth. Another question from the chat here, it's regarding the data again, and I know that you have said that you haven't seen much of the data, but the question goes: Were the test patients housed or were they simply tested outpatient? Were there any regional differences between the tests? Regarding tests now- Yes ...to understand, is it how the- Patient data injections have been done? Yeah. I mean they- And this- I mean, it's all, like, the same intranodal injections have been done in the same way. Obviously, there are many different clinics. In total, we have 57 clinics, Europe and U.S., but they've all been done by very competent personnel who know how to do this. It's a relatively simple procedure. It is outpatient procedure. You don't need to be hospitalized, which is also important here. Ultrasound-guided, and as I understand, all the individuals who do the injection, they keep also, like, a log or, like, a diary where they write the success if. There's no indications that we have received that there would be, like, a large amount of injections that have, like, failed. We will be able to look to some extent on that kind of information as well when we have the antibody data, because we know when we inject with GAD, so our protein, you do get elevated GAD autoantibodies, and the placebo arm doesn't get anything. That's an important one of those important checks to make sure that everyone who was injected actually got this antibody response as well, and placebo didn't. There's a lot to look into, but there's nothing, as we know, as of yet indicating that there would be any differences. Again, on the subgroups, pre-specified subgroups, there's to some extent some, like, you do a stratification on regions, for example, Europe versus U.S. Again, there's nothing that we can see that worked in one place and didn't work in the other place. Surprisingly flat across the board. Nothing. Regarding scenarios again, what would need to happen for this program to remain viable, and what would need to happen for it to be effectively terminated? To be viable, I mean, obviously, let's if we talk about this specific trial right now that is ongoing, that would mean that we can see in this first stage of analysis that there was something in the analysis that was done wrong. We can repeat the analysis, let's say the right data files or there was something in the statistical programming or something like this. If that would be, and you can repeat the analysis and see you get a different outcome, in that case, you can then continue the trial because, again, we are on a very limited basis, unblinded currently. We haven't really on purpose dug deeper. But that would be and that would mean then that the trial can continue. The other one would be if we see that everything has been done correctly or the results that we see now are the truth, why they look, we still need to figure out. In that case, we most likely will then take the decision to discontinue the trial in a very controlled manner. Again, you need to do the safety follow-ups for patients and so wind it down in a very controlled manner and in discussions with regulatory agencies. Then in parallel, do all of the analysis to understand the data at hand because that will then inform the next steps regarding the development of the investigational drug. To sum this up a little bit, I have a last question for all three of you here. It's been a turbulent weekend, very surprising results that you have gotten, but do you have any message you would like to convey to diabetes patients, your shareholders, or the market? If we start with you. Yeah. Well, obviously big disappointment. I'm not sure which camera I should be looking at here, but- Look at the- ...yeah, the middle one, number three. Big disappointment for us, and I understand for shareholders, for patients, for clinics. We obviously hope that we come to the root cause of this to really understand. We obviously, as a company, believe in this, and I know there are many others who believe in this, but we have to be honest as well that we need to understand the data before we can sort of take next steps here. From a shareholder perspective, I completely understand. I mean, the share is doing terrible currently, understandably so. It's our job now to try to sort of get back the trust from shareholders by doing the best possible work right now in figuring out the current data and also working in parallel with strategic options to again in the best way possible, I mean, increase share value here, which, again, I'm saying I understand 80%-90% down in share in a single day. It's difficult to stand here as a CEO and talk about shareholder value, but I feel it personally. I know there are others out there that feel it even much more from an investment perspective. We try to do our best, and that's the only thing we can do. Josh? I would just say, you know, one question I was asked this weekend is: How big of a setback is this for the field? I would say this is certainly a setback for this particular trial, but not for the field overall. You know, these moments are difficult, but they sharpen our understanding, and they accelerate the better designed approaches and more targeted application of therapies that are currently in development. I would say that the field is stronger today than it was even a few years ago. We have clearer staging of disease. We have an increasing focus on precision medicine approaches. There remains a need for an unmet need for safe, effective therapies that are able to rebalance the immune system in type 1 diabetes. Diamyd is a pioneering approach for precision medicine in this space, and the analysis that needs to come over the next few weeks will be critical not only for determining the next steps for Diamyd, but for using the insights gained to hone precision medicine approaches in type 1 diabetes overall. We are committed to work with the Diamyd team as they go through this process. I'll say the board and management of Diamyd, many of them either have type 1 or have loved ones with type 1. This remains and is always a focus that we're doing efforts that not only help the community, the global community, type 1 diabetes is a global disease, but we're also doing it to help our loved ones. You know, there's no question that this group is passionate about where it's going, and we will just continue on this journey. Thank you very much, Ulf. Thank you very much, Mark and Dr. Vieth, for taking the time to talk to us, and thank you everyone for watching. We will be waiting for further updates from you. Thank you. Thank you. Thank you. Thank you.