Please advise that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Anne Doering. Please go ahead. Thank you, Sonia. Good afternoon, and thank you for joining us today for the company's R&D update conference call. This morning, Vivoryon issued a press release announcing new data showing unique treatment effects of varoglutamstat on kidney function in patients with diabetes. Importantly, and due to this data, the company is also outlining the proposed clinical development plan in diabetic kidney disease or DKD. This press release is posted on the company's website at www.vivoryon.com. Before we start, I would like to remind you that during this conference call, we will present and discuss certain forward-looking statements concerning the development of Vivoryon's core platform, the progress of its current research and development programs, and the initiation of additional programs, as well as results of operations, cash needs, financial conditions, liquidity, prospects, future transactions, and strategies. Should actual results differ from the company's assumptions, ensuing actions may differ from those anticipated. You are therefore cautioned not to place undue reliance on such forward-looking statements, which speak only as of the date hereof. On the call with me today are Vivoryon's Chief Executive Officer, Frank Weber, and Michael Schaeffer, our Chief Business Officer, who will be available for questions. We will begin today's call with opening remarks from me, then move to Frank's discussion of Vivoryon's clinical updates on varoglutamstat, our lead asset, where he will speak about the promising data in kidney disease, particularly in a diabetes subgroup, and the proposed clinical development plan in DKD. After that, I will conclude the call with an overview and summary. Following the prepared remarks, we will host a Q&A session. We are excited to be entering a new era of R&D focused on kidney disorder therapies. As a reminder, in a pre-specified endpoint analysis in our VIVIAD phase IIb study, we have already shown you that under varoglutamstat treatment, there is a significant kidney function treatment effect. We see a statistically significant and clinically meaningful change in the estimated glomerular filtration rate, eGFR for short, of 3.4 mL/min in the overall VIVIAD phase II study population. Importantly, we observed a robust and consistent effect across various methodologies and analyses. For example, calculations of eGFR over two years, as well as using multiple methods and approaches. As we have shown before, we see excellent tolerability. As you can see, all of this was already very encouraging, but today we have particularly exciting news to share. Building on the solid dataset from the overall VIVIAD study population, we are thrilled to report truly compelling data from the diabetes subgroup within the VIVIAD study. The treatment effect of 8 mL/min observed under varoglutamstat treatment in this subgroup was substantially higher than in the overall study population. This improvement is statistically significant and very exciting. Additional potential health benefits were also observed, with a trend for improving the levels of certain liver enzymes, mild weight loss, and lowering of diastolic blood pressure. On the safety side, we continue to see a great tolerability profile, with comparable adverse event rates in the diabetes subgroup versus the total study population. These data lead to a clear pathway for varoglutamstat to advance in DKD. What this means now is that we are planning to complement the data available to date with a new phase II study of varoglutamstat in advanced, meaning stage 3b 4 diabetic kidney disease, with treatment being administered on top of standard of care for DKD. This is subject to further funding or partnerships. We also plan to conduct non-clinical and mechanistic studies in parallel, which will enable us to prioritize potential additional indications for clinical development. So with that, I will now turn it over to Frank to walk you through the details of the data and the proposed clinical development plan. Thank you, Anne, for this nice introduction. Good afternoon, good evening, good morning, ladies and gentlemen, wherever you're listening. My name is Frank. I'm the CEO of Vivoryon. The following 20 charts, we will present you in detail the kidney results of the VIVIAD study with a very special focus on patients with diabetes. Before going into the results, this slide shows a summary of the study design. The VIVIAD study was carried out in patients with early Alzheimer's disease and primarily designed to investigate cognition. The kidney function was inbuilt into the protocol as a pre-specified endpoint. Because there was strong evidence from preclinical data that varoglutamstat can improve kidney function. 259 patients were randomized into the VIVIAD study between placebo and varoglutamstat at a dose of 600 mg twice daily after the DSMB has confirmed that this dose was safe. Another important design element of the study was that the treatment duration for each patient was defined as up to 96 weeks, but that the study ended for all patients, and the last patient randomized completed 48 weeks of treatment. In total, there were 32 patients with diabetes included into the study... Here we show the baseline characteristics of the patients, of the total population of the study, as well as of the diabetic patients on the right side. Patients had an average of 69 years of age and were balanced regarding gender. The majority of patients had an estimated glomerular filtration rate at baseline between 60 mL/min-90 mL/min, and the mean eGFR was 82 mL/min for the total population, and similar in the diabetes population. The HbA1c at baseline in the diabetes population was 49 mmol, so it was a very well-controlled patient group. Some may just have had a mild version, so-called pre-diabetes. About 90% of the patients had type 2 diabetes. Also, the blood pressure was very well controlled in the overall population, as well as in the patients with diabetes, with approximately 135 mmHg- 80 mmHg, systolic and diastolic blood pressure in average. Here on this slide, we present the concomitant medication at baseline, which the patients in the diabetes group had. Patients in the diabetes group had multiple treatments to control the blood sugar levels. In average, 1.5 medications per patients, including metformin, gliptins, SGLT2s, and semaglutide. For controlling the blood pressure on the right side of the chart, patients in average received also 1.5 medications. Specifically, the majority received drugs addressing the renin-angiotensin system, and also the majority of patients received lipid-lowering concomitant medications. In summary, the patients, which all were recruited from Western European countries, including Denmark, Netherlands, Germany, and Spain, had a typical and adequate standard of care for the diabetes, kidney, and blood pressure. As pre-specified in the study protocol, and here we come to the efficacy results now for the kidney. As pre-specified in the study protocol, the estimated glomerular filtration rate was first calculated in the overall study population, using creatinine as a parameter and applying the MDRD formula, which is a gold standard in assessing kidney function. The difference between varoglutamstat group and placebo group was calculated applying a slope analysis, taking all available data points on treatment into account. This methodology is standard in science and with regulatory authorities like the FDA and EMA. The difference between varoglutamstat and placebo was 3.4 mL/min per year in the overall VIVIAD population, and highly statistically significant with a P value of 0.001. You see this in the middle of the triptych on display chart on the left side, the dark blue bar. That's the difference between active and placebo. In the diabetes group, which you find in a lighter blue on the right side, in the diabetes group, the difference was much higher, with 8.2 mL/min per year, and also statistically significant, with a P value of 0.02. On the right side of the slide, the slopes of varoglutamstat in blue and placebo in orange are displayed, so that for transparency, everybody can track the evolution of the eGFR over time. And we display it here for both the total population, which is the upper chart on the right side, and the diabetes population, which is the lower chart on the right side. The little dots on the graph show the point estimates at each study visit. It is very evident that varoglutamstat improves glomerular filtration rate versus baseline and compared to placebo in the overall population, and even more in the diabetes group. The improvement of the glomerular filtration rate, and this is, the new chart now, compared to placebo, was also significant in the total population and in the diabetes population, when we co-calculated the eGFR with cystatin C as a parameter and the CKD-EPI 2021 formula. It's again, a gold standard in science and typically done when assessing eGFR. Again and consistently, the effect size was larger in the diabetes population compared to total study population, and again, it was significant both for the total population and for the diabetes patients. Subsequently, we also analyzed the treatment effect over time to understand, first of all, how quickly does the drug start to work, and secondly, how long does the effect last? You see here the results for the diabetes patients. On the background, you see the slope analysis, which we showed before in the previous chart, for the eGFR development in diabetes patients over time. As you see that the drug was up titrated to 600 mg in the first 12 weeks, in this period, there was no positive effect compared to placebo. Actually, it was a slight decline of eGFR, and that is indicated by the blue bar charts at the lower part of that graph. You see -2.2 mL for the first 12 weeks. At week 24, when patients were 12 weeks on the full dose of 600 mg, the improvement of eGFR was 5.3 mL in favor of varoglutamstat. This is approximately 50% of the full effect size. We then analyzed the period between week 36 and 84, where varoglutamstat consistently, clearly better performs versus baseline and versus placebo. For understanding the durability of the treatment effect, we pooled the results of weeks 36 and 84, and calculated a weighted mean value for the eGFR, which was a difference in that period of 9.8 mL/min in favor of varoglutamstat, and of course, highly significant. In a final step, we then took the results for the visit at week 96, if the patient were in the study until week 96, or at the last earlier time point, when it was the last treatment visit of each enrolled patient. We looked at the difference of the last time point of the patient on treatment, which is called EOT, end of treatment, and looked at the difference between varoglutamstat and placebo, and it was 8 mL/min. That is very similar to the weighted mean of the prior visits. It can be concluded that the treatment effect of varoglutamstat is durable for up to two years of treatment. Switching now to safety. Varoglutamstat was very well tolerated at the dose of 600 mg tested, and there were no statistically significant or clinically meaningful difference in the safety parameters between varoglutamstat and placebo in the overall population, and also no difference for key safety parameter in the diabetes group on the right side of this chart. There were no deaths reported during the study. We carried out also a detailed analysis for all treatment emergent adverse event and grouped them by so-called system organ classes for the total population and for the diabetes group. The results for the placebo group are displayed in the left side in orange, and the results for varoglutamstat on the right side in blue. The non-filled open bars show the number of patients with an adverse event in the total population. The filled smaller bars in the diabetes group. Firstly, event rates and distribution of events between organ classes are very comparable between varoglutamstat and placebo. And the numbers displayed here are patients who had an AE in a system organ class. Keep in mind that there were more patients on drug than on placebo for both the total population and the diabetes population. The most frequently reported adverse event were infections, and the vast majority thereof, COVID-19 infections, as the trial was conducted more or less completely during the COVID pandemic. Most importantly, and indicated here, are that there are no differences for the renal and urinary organ class system in the varoglutamstat group compared to placebo. The same is true for the metabolic organ class. Switching to the next slide, a diligent analysis was also conducted for proteinuria. The study protocol in VIVIAD included a dipstick semi-quantitative urine test. And on the left side of this chart, all urine tests for proteinuria, proteinuria, sorry, under treatment are displayed, and as you can see, the majority of patients had no proteinuria during treatment. The number of positive tests during treatment was comparable between varoglutamstat and placebo. We carried out an additional analysis on the right side of the slide to analyze sustained proteinuria, and that means that patient had at least three treatment visits during treatment with a positive protein result in the urine or a worsening under treatment. And there was no case of a patient who had a sustained proteinuria under treatment, who was not positive at baseline in the varoglutamstat group. There were single cases meeting this definition in the placebo group. Additional analysis were conducted for other relevant health outcome parameter in the diabetes group, comparing varoglutamstat and placebo. I want to highlight here, before going into the details, that for none of the parameter displayed here, a relevant difference was observed in the total study population between varoglutamstat and placebo. In the diabetes population, though, at week 48, patients lost about 4 kg of weight compared to baseline and placebo. This represents about a weight loss of approximately 6% in one year. Also, patients showed a decline in diastolic blood pressure of 6 mm Hg in the varoglutamstat group versus baseline and versus placebo. This is particularly important because it shows that no hyperfiltration is observed. Hyperfiltration means an increased flow of blood through the kidney, with subsequent increase in pressure on the kidney, which in the long term, will rather increase kidney injury than improve kidney function... The drop in diastolic blood pressure, or in other words, the drop in vascular resistance, demonstrates that varoglutamstat does not induce hyperfiltration. On the right side, a drop in transaminases are observed under treatment with varoglutamstat compared to baseline and compared to placebo. While patients generally had transaminases in the normal range at baseline, this finding is consistent with prior research evidence that varoglutamstat has a positive effect on the liver in non-alcoholic fatty liver disease and in NASH models. It also shows that varoglutamstat has definitely no adverse event on the liver function. Finally, it was analyzed whether the beneficial effects described so far were induced or correlated by an improved glycemic control, or whether varoglutamstat has a direct or indirect effect on blood glycemia. This is clearly not the case. As it can be seen on the left chart, the HbA1c was completely stable during the study period, versus baseline in the blue line, which represents varoglutamstat. The placebo group showed a minimal improvement, which also proves that the beneficial results versus placebo observed in the varoglutamstat are not related to a poor glycemic control in the placebo group and due to diabetes progression in the placebo. What was observed in the varoglutamstat diabetes group was a very marked and pronounced reduction of pyroglutamyl-CCL2 versus baseline and versus placebo. Pyroglutamyl-CCL2 is a very potent inflammatory peptide and cytokine. This was highly significant, with a p-value of 0.004, and you see it on the right side of the chart. In summary, concluding the results, varoglutamstat has a unique profile, leading through a potent anti-inflammatory mechanism to a sustained and durable improvement in kidney function, accompanied by additional beneficial effects on weight, blood pressure, and liver function. We now switch the section, and we will unveil how Vivoryon plans to seize this unique opportunity in kidney disorders and specifically diabetic kidney disease. Diabetic kidney disease is the leading cause of chronic kidney disorders and end-stage kidney disease on a global scale. Worldwide, in 2021, there were estimated 537 million patients with diabetes, and in the core markets of the larger U.S. and Europe, approximately 112 million of out of these 537 million. 40% of these patients have or will develop diabetic kidney disease, and 10% have or will develop end-stage kidney disease. So there are estimated approximately 11 million patients in the larger U.S. and European market with end-stage kidney disease in 2021. Due to this enormous medical need and also the high costs associated with the treatment of end-stage kidney disease, notably, many patients will require either dialysis or transplantation. Significant investments were made and new medications developed in the past by other pharmaceutical companies. Within those newly developed drugs, sits a class of products called SGLT2 inhibitors, that work by inhibiting the glucose reabsorbed in the kidney and improve glycemic control, while reducing the progression of the kidney worsening and reduce also cardiac events. Similarly, recently, Semaglutide has shown in the FLOW study to reduce progression of kidney dysfunction and improve cardiac events. On this chart, you can see the effects of these improved and well-known drugs on the eGFR and the kidney function. The improvement versus placebo for these drug classes range between 1 mL/min and 1.6 mL/min per year, resulting in a further progression of kidney dysfunction, though at a reduced level. Varoglutamstat has a completely different profile. The drug improves eGFR versus baseline, and what is also noteworthy here is that the placebo group in diabetes patients in the VIVIAD study showed a nearly identical progression pattern compared to semaglutide placebo group in the FLOW study and the dapagliflozin placebo group in the DAPA-CKD study. These are the orange bars on the bar chart. While cross-study comparisons are always tricky, these data show clearly that the treatment effect observed with varoglutamstat was achieved in a population with a typical kidney progression pattern, which you see in diabetes patients. Moving forward, we also analyzed the effect size of varoglutamstat, depending on the baseline severity of the eGFR. Nearly identical effect sizes were observed, as shown on the left side of the chart. What is missing in the VIVIAD population are more advanced patients with diabetic kidney diseases, meaning patients with an eGFR between 15 mL/min and 45 mL/min, which is shown in the blue rectangular part of the graph on the right side. We therefore plan to investigate the effects of varoglutamstat in this more advanced DKD population in the new phase II study before embarking into confirmatory phase III development program. The design of this new phase II study includes diabetes patients with stage 3b 4 CKD, and a high amount of proteinuria. That is a patient group which is at highest risk to progress fast to end-stage kidney disease. This double-blind, randomized, placebo-controlled study is planned to include up to 120 patients, being randomized 1:1 between varoglutamstat and placebo, with a treatment duration of 15 months. With 120 patients, there will be an 80% power to detect the 5 mL difference of eGFR between groups. Additional endpoints will be the albumin-creatinine ratio in the urine, biomarkers of inflammation and fibrosis, as well as parameter for measuring the liver function. In parallel, we see also a great opportunity to advance varoglutamstat into orphan kidney disorders. Their progression of disease is associated with a significant degree of inflammation and fibrosis. The target here is to stabilize kidney function in these patients. Disorders we are targeting are Alport syndrome, a disease with currently no specific treatment, and Fabry disease, specifically in male patients showing kidney progression under enzyme replacement therapy. The advantages in orphan diseases are well known, are a faster time to market and smaller study sizes. In my last slide, I want to emphasize that the results shown here in this webcast, the first time in patients, are based on a decade-long research and development activities, with publications already having demonstrated the beneficial effect of QC inhibitors on kidney and liver function, including models of glomerulonephritis and non-alcoholic fatty liver disease. So the results we present herein are not a surprise, they're based on meticulous research activities. To continue this effort, we have already started and initiated additional research and non-clinical pharmacology studies to further generate data in diabetic kidney disease, orpharn kidney disorders, and the profound scientific investigations of the mechanism of action and underlying pathways. With this, I hand back to Anne for the closing remarks. Thanks, Frank. As I mentioned in our last call in May, we are active in building a presence with scientific and medical key opinion leaders in the nephrology community. Today, we'd like to introduce to you some of the key experts we are working closely with and who are supporting all aspects of our kidney disease strategy. We are proud and appreciative to be able to work with these seasoned experts on creating the ideal path forward for varoglutamstat in kidney disease. Tobias Huber is Chair of the Center of Internal Medicine at the University Medical Center Hamburg-Eppendorf in Germany. He is acting as medical advisor for clinical study design, and we are happy to announce a research collaboration with him and his team, focusing on preclinical and mechanistic activities relating to varoglutamstat and the role of QPCTL on kidney function. We also would like to work with Florian... We are working with Florian Jehle, CEO of Vifor FMC Renal Pharma. He is acting as an industry expert advisor to us in the kidney field, including providing strategic business and commercial advice. Kevin Carroll, the CEO of KJC Statistics. He is providing statistical analysis and advising on clinical study statistical aspects. We look forward to working closely with Tobias, Florian, and Kevin as we build on this great initial data in DKD to craft an impactful clinical development strategy for varoglutamstat in this area of high unmet medical need. I would now like to wrap up our call with the key elements we believe we have in place as we move forward with the company's strategy in kidney disease. We continue to be very excited about the strong kidney data we have presented to you over the past few months and today. These data reinforce our strategic shift to focus on kidney disease, and we see today's report as a further step towards securing the company's future and creating shareholder value. Furthermore, we believe varoglutamstat has the potential to be the first oral treatment specifically aimed at improving kidney function on top of standard care. To recap, we have compelling efficacy and safety data in people at risk of kidney disease, where we have demonstrated a statistically significant effect on kidney function in the total VIVIAD study population. Today, we have corroborated this data and have shown you the additional VIVIAD analysis, showing a highly compelling improvement of kidney function in the diabetes subgroup. Varoglutamstat is also well tolerated. You have seen the proposed clinical development plan aimed at effectively targeting the large unmet need in DKD. 40% of people with diabetes may develop DKD, and kidney function continues to decline despite new therapies. Our plan is for a placebo-controlled phase II study in the stage 3b 4 DKD disease patients on top of standard of care, subject to further funding or partnerships. We have a clear strategy for building evidence, including an additional kidney disorder. We have established collaborations with industry leaders and kidney specialists, and continue to expand our network in the field. We anticipate further kidney function data from VIVA-MIND study in early AP and second half of this year. Also important, we continue to investigate the mechanism of action, as well as the potential for QPCTL pathways in kidney disease and other indications. The company's activities are aimed at securing all aspects to support future growth. Our foundational composition of matter patent runs to 2031, with additional potential for Hatch-Waxman extension of up to five years. Further filings extend our potential patent protection to at least 2044. We are actively pursuing funding and business development opportunities to fully execute a phase II DKD study. We look forward to keeping you updated on our progress as we continue to move forward with our strategy. With that, we will now open the call to take questions. Let me allow a final comment, and I want to thank the Vivoryon team wholeheartedly for their diligence, and I would say, huge efforts to get us there. Specifically, I want to mention Christine and Lauren, who have worked so hard on this presentation and the data and enabled that presentation today. Thank you a lot. Let's go to Q&A, please. Thank you. As a reminder, to ask a question, you will need to slowly press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. We will now take our first question. Please stand by. The first question comes from the line of Lucy Codrington from Jefferies. Please go ahead. Your line is now open. Hi there. Thank you for taking my questions. So just a few. Just to confirm, the 20 patients, were they all on 600 mg of varoglutamstat? Secondly, it doesn't look like any of the patients on varo actually had stage 3b or 4 kidney disease. So what is your level of confidence that you would be able to move straight into a phase II within this population? Any concerns there? And then I guess related to that, have you sought any regulatory feedback on your development plan? And I guess just generally, what's your-- I appreciate the data look compelling, but we are talking very small patient numbers here. So I guess, what's driving your level of confidence and, you know, supporting, prioritizing this indication over potentially an orphan indication, whereby, as you said, the timelines are quicker, the pricing is higher. You know, is that not, you know, a potentially more sensible route, particularly given the, you know, increasing evidence supporting the benefits of GLP-1 within the diabetes population? You know, there's only kind of 10% of patients on a GLP-1, and this is that reflective still of what we would expect to see in a clinical trial now. And then just to confirm on that, the 10% on SEMA and the 10% on SGLT2 in the vara group, what was that in the placebo group? Thank you. There's a lot of questions. Let's start. 600 mg are confirmed. Patients initially could have been on 300 mg, but they switched to 600 mg at the end. Second, there was the question on what was this? The confidence level. Why are we confident? First of all, we started with the total population, and the total population is significant and shows the same pattern, an improvement above baseline and an improvement versus placebo. It's just that the magnitude of effect in diabetes patients is higher, and we see other things happening in diabetes patients we don't see in the total population. You simply can come up from the principle that if there is more inflammation, which diabetes creates on the organ system, both on the vascular, on kidney, and on the liver, the better the drug works. So we are, I would say, relatively confident, strongly confident. The other thing is, this is small patient numbers. Yeah, but because it's based on the bigger population where we see the same thing, it's just a matter of effect size. And when you have a big effect, you need relatively small patients. If you have a small effect, like a mililiter difference, like you see in the typical SGLT2s or others, you need 2,000 patients. If you have 8 mL difference, you probably need 40, 50 to see that difference. If the effect is consistent and over time, the same, and patients all react the same way. So there's limited variability, and that's what we have here. So we are very confident. Then, patients in the placebo group were very similarly treated with the active group, and you see that also because they decline in the placebo group, which we have reported is very similar to what you see in semaglutide or the DAPA study in a corresponding population, and that was your other question. Not all the semaglutide and the DAPA studies were done in very advanced patients. They were done in patients with mean between 50 and 75. So it's not necessarily that all the diabetes studies are done in late-stage patients. I think, and in the end, I think there is a little bit of misunderstanding. We start in a phase II study, which is usually an exploratory non-confirmatory study, just to add the data in more severe patients. We need to know this. We cannot leave that open. I think that would be a mistake. But in parallel, we of course qualify, and I tried to say that, for, for orphan indications like Alport and Fabry. Now, we, we always were a very systematic company, and that means that we do pre-clinical experiments before we do clinical ones. So we're going to run some organ studies in Fabry and run some organ studies in Alport before we embark in a clinical program. And there is on the charts, I didn't say about this, but it's on the charts. There's still the basket study, orphan diseases up to 60 patients, which is another phase II study, depending on financing, we can run. So I think it is a misconception that we already decided that we run to, to the market, to phase III, completely from now in DKD and see what's right and left. What we try to say is, we need to run the phase II study in DKD in order to design a phase III program in DKD, and at the same time qualify orphan indication, which is the most promising, and then advance there. The final decision, where to go and how to do it, depends, of course, on the data we generate from now on this. I hope that has a little bit clarified the tonality. Thank you. We will now take our next question. The next question comes from the line of Christian Ehmann from Warburg Research. Please go ahead. Your line is now open. Hello, and thanks for giving us the interesting update for your VIVIAD. So I was looking at the standard deviation for the glomerular filtration rate at the beginning, and we already see very high standard deviation in this area. And a little bit too, my question goes into the same area as my colleague. So, given that we have highly pre-treated patients here and we see the high standard deviation, what kind of patients are you looking for when you try to design the trial? And what kind of pre-treatment would you say were eligible for inclusion in your trial? Thanks. First of all, there cannot be a high standard deviation because there wouldn't be P values. You can only have, have P values if the confidence intervals don't overlap. You cannot have P values in 250 or 30 patients, which where the confidence interval are not extremely far away. Of course, eGFR is not an extremely precise instrument to measure kidney function. It has nothing to do with the filtration. It has to do something that the patient is a little bit different every day. But you see consistently in the data we present, that the active arm is always better than placebo arm, and always by a magnitude. The active arm never drops below the baseline. The placebo never drops above, it goes never above the baseline, and there is always more than 5 mL difference at each time point of measurement once you're on the plateau phase. Of course, not in the beginning. So that is the first thing. The second thing, and that is the answer when you go into the trial I presented on semaglutide. Totally on the left side, you find a study of data in more advanced patients. And typically, what you do in more advanced patients is that your placebo group progresses more. And you can look at other companies who are currently running three and four phase II studies. Typically, you se e probably a four-five, sometimes even a 6 mL/min per year decline in those more advanced diabetes patients with a high degree of proteinuria. The variability is not very high. As you see in this graph, where we put all the relevant trials in one graph, the placebo group behaves very predictable and very similar. It's not that usually there's approach, surprise and say, "Ha, we have only 1 mL or we have 7." Usually, you see something between a 3mL and 5 mL decline, depending on the severity of diabetic kidney disease. And if you are aiming to stabilize the disease or slightly improve it, which we can show with our compound, I don't think we have to worry so much about variability. So it's always a risk, but I'm... Given the big effect size you're looking at, I'm less worried, I have to say. We can always do a new study that is not decided yet, as a futility analysis or a sample size readjustment analysis, based on the decline in the placebo arm which we observe. So basically, you say your prediction is the placebo group drops by 4 mL/min per year on average, and you can control for this in a blinded analysis to make sure that your placebo group is performing as by the books. And then you are basically okay, and then you can see how well your drug is performing as a placebo group. So I'm for the design of the new study, I'm not so worried here. Did I answer your question? Yes. Thank you very much. Thank you. We will now take our next question. Please stand by.... And the next question comes from the line of Luísa Morgado from Van Lanschot Kempen. Please go ahead. Your line is now open. Hi, team. Well, first of all, congrats on this data, and also thank you for the thorough analysis on it. I wanted to ask if you could first elaborate on the non-clinical and mechanistic. If you already touched a bit upon it, if you could elaborate a bit on those studies that you mentioned would be conducted for additional disorders. And of course, once again, if you could just remind us. So I'm guessing Fabry, and what other disorders would be possibly the most obvious step? Yeah. So you work really hard to understand, but what I conclude is that you want to know what we—what type of pharmacology studies we do. I mean, when you look into models of kidney disorders in diabetic animals, there is a number of standard models you do, like db/db, db/db mice, streptozotocin-induced kidney nephropathy, and so on, other things. And we currently run all those also to understand the exact mechanism and this cascade of mechanism downstream of pGlu-CCL2 and potentially other, other effects. Because with pGlu-CCL2, we can explain the kidney, we can explain the diastolic blood pressure, we can explain the liver, but not necessarily we can explain the weight loss. So there is probably something else happening there, and we need to better understand that, and therefore that, the animal models are there. Then, of course, we need to run some probably more organ-on-a-chip models than complete animal models into some orphan diseases to prioritize and understand the exact mechanism of action of the drug there before we embark into clinical studies. That's probably what we're gonna do. Okay, very clear. In terms of the phase II trial costs, do you have any estimation for that? Beyond that, in terms of scenarios from here onwards, in securing that funding, of course, what are the different scenarios that you are outlining? Thank you. So what, I mean, of course, we looked at cost of that study, and we are in the range of EUR 10 million-EUR 12 million for a study, which we basically showed here. And we have also some quotations in-house. This is typically what you would expect in that thing. Then the other question, I didn't really understand, but where we go from here, or what was the question exactly? What you want to know? More in terms of, of course, in terms of raising or partnerships, what are the different scenarios, well, that you're trying to, that you consider in terms of being able to fund this, this trial and moving forward with the rest of the development plan? Yeah, I mean, all doors are open, I would say. We will look at all avenues and see what is the in the best interest of the shareholder and the value of the company. There is at current stage, we are basically modifying our R&D target. It's not a rebirth because it was always there, but we are shifting emphasis to more the inflammatory fibrotic pathway. Of course, we are looking at interested parties at all levels. Yeah, I think more I cannot say currently. Okay, thank you so much. That's all from my side. Thank you. As a reminder to ask a question, you will need to press star one one on your telephone and wait for your name to be announced. We will now take our next question. The next question comes from the line of Joseph Hedden from RX Securities. Please go ahead. Your line is now open. Hi, good afternoon. Thanks for taking my questions, and congrats on this very interesting data. I just wanted to pick up again on the BD point there and the funding of the trial. So you've known for a while that there's been a positive effect in kidney diseases, and you've informed us very well that you're kind of looking at target indications. You've come up with that information. In the period of, you know, that time, did you have any kind of interesting discussions in business development with potential partners? And has any seen these data already? Is there anyone on the hook that this plan could now just perhaps tip over the edge? Or is it a case of now you have the package that you can actually kind of go, go out and present the plan to potential partners? And that's the, that's the first thing. The second thing is just on, as part of this kind of, you know, redirection of, of the development program to very great and that, and the emphasis on kidney disease. So are all the cost savings that you could possibly make in other areas, but have they been implemented already at this point? Thank you. So probably on the BD part, I mean, we are in contact with companies, but the data we presented today are new, and we haven't presented to anybody else. And they are, of course, an evolution from what we presented in the past, but now we have a lead indication, and we have a very specific benefit. And so that is still then to be rolled out further to interested parties. And I think I stop here. On the financials and how are we doing? As far as the cost savings concerned, as you can imagine, we're always looking at ways to save additional costs and ways to prioritize our funding and our projects. So that's how I would summarize it. Yeah. There's also no update on the runway or something like this. I mean, we save unnecessary costs in some areas, whereas of course, we start investing in kidney disorders more heavily, so it's not that we have a no investment policy. We need to move forward in kidney, and we need to generate some more data as outlined, and that is all covered and funded so far. Okay. So, just on the runway, the runway remains, you know, as you previously stated, I think, into next year, and obviously, this phase II trial is subject to additional financing and development in other orphan indications, those preclinical models, is that subject to additional financing as well, or is that built into the plan? So there are certain elements... I mean, our runway remains the same. We've been consistent with that and with that language for the last few calls, and that doesn't change today. I think we've also indicated in the past that some of that budget, as we look to reprioritize some of the funding, some of those studies that we do have, the non-clinical studies are covered, or captured in that cash runway. Okay, thank you very much, Lisa, and thanks, Frank. Thank you. As there are no further questions, I would now like to hand back to Frank Weber for any closing remarks. Yeah, thank you. And addressing all what we have heard, it is not that we weren't concerned when we saw the data, and that is not that we scratched our head and say, "Is it true?" And as a matter of fact, we remeasured creatinine clearance and eGFR three times. We took three different samples of patients. We took different lab equipment. We measured again and again and again, and we found consistently the same results. It is not that we cherry-pick here. We also put all the creatinine data we ever measured in one single database and looked at the means there and see whether the results were confirmed. So not picking one over the other, and we always see the same thing. Regarding the subgroup of diabetes patients, of course, we scratched our head and say, "Is it chance? Is it true?" But we ran other subgroups. Subgroups of patients with hypertension and with cardiac diseases, which are ever even more higher numbers than in the diabetes group. These subgroups, interestingly, didn't deviate from the effect of the overall population. In other words, we see in hypertensive patients who have no diabetes, the same effect size as we see in the overall population. The diabetes patients shine out and are different, and we're going to try to understand exactly why that is and how that is and how big that is. It is clear that hyperglycemia introduces inflammation and chronic inflammation on a lot of tissues, and that contributes to the development and advancement and progression of the disease. We have proven evidence with the pyroglutamyl-CCL2, too, that we counteract that inflammatory fibrotic pathway very potently. I think that is an excellent lead to believe and think that the data we presented today are very transparent and true. With that, I thank you for the attention and hope to see you the next time. Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect. Speakers, please stand by.