Julia Neugebauer: Good afternoon, and thank you for joining us today to discuss the company's first half 2025 results and operational update. This morning, Vivoryon issued a press release reporting its first half 2025 financial results and also share an update on the progress we're making in advancing Vivoryon within the kidney disease space. This press release is posted on the Vivoryon's website at www.vivoryon.co. On the call with me today are Vivoryon's Chief Executive Officer, Frank Weber; Vivoryon's Chief Financial Officer, Anne Doering; and Vivoryon's Chief Business Officer, Michael Schaeffer. I will begin today's call with an overview of the unmet need in kidney diseases and highlight our most recent key achievements. I will then hand the call over to Anne, who will review the first half 2025 financials. After that, Michael will provide insights into new mechanistic in preclinical data supporting the development of varoglutamstat in diabetic kidney disease as well as in rare kidney diseases. Finally, Frank will wrap up the call with a summary and an overview of the next steps to advance our strategic priorities. Following the prepared remarks, we will host a Q&A session. 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 development programs and the initiation of additional programs as well as a results of operations, cash needs, financial conditions, liquidity, prospects, future transactions and strategies. Should actual results differ from the company's assumptions, ensuing actions might 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. Our aim at Vivoryon is to transform the treatment of kidney disease. Despite recent advances in the field, there remains a significant unmet need for effective treatments for kidney diseases including chronic kidney disease and diabetic kidney disease. These conditions often progress to end stage kidney disease and kidney failure. Current standard of care therapies can only slow disease progression, they cannot pause it or improve kidney function. Chronic kidney disease is not only a growing global health challenge but also one of the largest unmet medical needs. By 2040, it is expected to become the fifth leading cause of years of life loss worldwide, underscoring both the human and economic burden. Chronic kidney disease is marked by a steady decline in kidney function, often leading to disability in premature death. Diabetes is a major driver with diabetic kidney disease being a leading cause of end-stage renal failure. Importantly, inflammation is a key pathway driving disease progression. This represents a critical area where innovation could really change the standard of care and where we are focusing our efforts with varoglutamstat. Taken together, these dynamics highlight a significant opportunity for new therapies that address the underlying biology and position us to make a meaningful impact in a large, growing and underserved market. The last 2 years have been pivotal for Vivoryon as they market the transition into a company focused on development of varoglutamstat for patients living with chronic and diabetic kidney disease. As many of you know, varoglutamstat is an oral first-in-class potent in selective QPCTL inhibitors designed to prevent inflammatory and fibrotic processes by blocking pyroglutamate formation. It has demonstrated outstanding benefits on kidney function in Phase II clinical studies and is uniquely positioned within the evolving kidney disease landscape. In 2023, we laid the groundwork by amending the VIVIAD study protocol to include kidney function biomarkers. This decision was driven by a strong scientific rationale to explore varoglutamstat beyond our industry focus on Alzheimer's business. In 2024, we generated exciting data. Kidney function benefits were first observed in the VIVIAD Phase IIb study with particularly strong effects in the diabetes subgroup. These results were further confirmed in the VIVA-MIND study and the data were presented at the ASN Kidney Week last year. We're very well received by the nephrology community. Building on this foundation, the first half of 2025 was marked by several important achievements. We presented compelling kidney function data, including a meta analysis from our 2 Phase II studies, VIVIAD and VIVA-MIND in an oral presentation at the European Renal Association Annual Congress 2020 side. Across all analysis, varoglutamstat consistently demonstrated statistically significant and clinically meaningful improvements in kidney functions compared to placebo. We secured a new U.S. composition of meta patents for varoglutamstat, supporting market exclusivity through 2044 with the potential for further extension. Complementing the clinical data, we also showed a synergistic effect when combining varoglutamstat with an SGLT-2 inhibitor in a preclinical model. And today, we will show new preclinical data from a diabetic kidney disease mouse model further validating varoglutamstat mechanism of action in diabetic kidney disease. Preparations for a dedicated Phase IIb study of varoglutamstat in patients with diabetic kidney disease are already well underway. And finally, we nominated our QPCTL inhibitor VY2149, which has an improved pharmacokinetic profile as a potential follow-on compound for development in DKD, CKD and rare diseases. Together, these achievements highlight both the near-term clinical opportunities for varoglutamstat in kidney disease and the long-term potential for our approach. And with that, I'd like to hand the call over to Anne for the financials. Anne?
Anne Doering: Thank you, Julia. I will now walk you through the first half 2025 figures. Research and development expenses amounted to EUR 2.8 million in the first half of 2025 versus EUR 10.3 million in the first half of 2024. This reduction of EUR 7.5 million was largely attributable to a decrease in clinical development costs from the VIVIAD and VIVA-MIND studies as well as a reduction on production costs. R&D expenses in the reporting period mainly occurred for kidney-related research. We have seen a decrease in G&A expenses with costs of EUR 2.8 million in the first half of 2025 compared to EUR 3.5 million in the first half of 2024. The decrease of EUR 0.7 million was mostly due to lower personnel costs and a decrease in legal and consulting costs. All of this resulted in a net loss for the first half of 2025 of EUR 5.5 million compared to EUR 13.6 million for the first half of 2024. The company held EUR 4.8 million in cash and cash equivalents as of June 30, 2025, compared to EUR 9.4 million as of December 31, 2024. We have maintained our cash runway into January 2026, which does not include any funds from the standby equity purchase agreement announced in April 2025. As of today, we have not initiated any tranches of the SEPA. Our spending plans continue to support the kidney disease strategy and the strengthening of our intellectual property position. And we continue to actively pursue additional financing and partnership opportunities, primarily to fund the Phase IIb study. Now I would like to take this opportunity to update you on a temporary change in the finance team. I will be taking a temporary partial leave of absence from the CFO role in the coming months to attend to a serious family health matter. Vivoryon's continued success and the company's stability and continuity are crucial to me. And therefore, I am pleased to announce that during this period, Marcus Irsfeld will assume the role of acting CFO, ensuring this continuity in financial operations and supporting the company's strategic objectives. Marcus is an experienced health care finance executive and CFO, who has been supporting Vivoryon as a consultant since the end of 2024 and will require little effort to ramp up on the CFO task. This is a solution that I believe strengthens the finance and Vivoryon team. Activities will continue uninterrupted during the period of my temporary partial leave, and we will work seamlessly together. Marcus brings deep life sciences expertise, including 5 years as CFO of iOmx Therapeutics. He has led companies through all stages of growth from founding and early-stage financing to exits and M&A. We would like to welcome Marcus to our core team, and we look forward to the added knowledge and experience he will bring to the management team. I'd now like to hand the call over to Michael Schaeffer, our Chief Business Officer, to provide insights into new mechanistic and preclinical data for varoglutamstat.
Michael Schaeffer: Thanks, Anne. Yes. Welcome, everyone, and thank you very much Anne for your words. Now let me continue with an update on the most recent R&D findings. Our lead product in development, varoglutamstat has a truly unique mechanism of action. By blocking the glutaminyl cyclase enzymes, QPCT and QPCTL, it effectively tunes down several proinflammatory and profibrotic signaling molecules by making them less active and stable. Now let me go a bit more into detail with this because the subcellular localization of these enzymes is also an important component in this context. Proteins and peptides are synthesized on the endoplasmic reticulum. Some proteins are already fully functioned active then. However, another set of proteins requires further shaping in a process for post-translation modification, which happens in the so-called golgi complex. You can see here the blue structure within the cell. And what's important for us now is that a small number of proteins like selected chemokines of the CCL family, namely CCL2, 7, 8 and 13 as well as some other chemokines and signaling proteins require the activity of QPCTL for further maturation. All these QPCTL substrates carry a specific signaling sequence, which guides them to the golgi, where QPCTL resides and where it catalyzes the formation of pyroglutamate forms or PE variants of these substates. Now why I'm telling all of this? I'm telling you this because any drug with a purpose to effectively inhibit QPCTL has to not only go into the cell itself, but within the cell, it has to enter the golgi complex as well. And that is what varoglutamstat does at the doses we have been testing. And we were able to show this very nicely with a new and highly sensitive assay we have developed recently. This method uses liquid chromatography and mass spectrometry, which has the advantage to make detection antibody specific for every single PE variant obsolete, saving a lot of time, money and providing increased versatility. We have been benchmarking this assay with VIVIAD study samples and can show you here that it's a 600-milligram dose, varoglutamstat effectively reduces pro-inflammatory cytokines pECCL2 and pECCL13 in plasma. And for pECCL2, the reduction was statistically significant. And we obviously were specifically interested in CCL2 as we have already seen and reported a dose-dependent reduction of pECCL2 in VIVIAD. So these changes are consistent with our previous analysis. And right here, as a reminder, we have shown this data to you before, the change from baseline at week 48 is depicted on the left on this slide. It correlates well with a dose-dependent improvement of the kidney function measured for eGFR in patients treated with varoglutamstat, shown on the right side. While this analysis here combines the values of study participants in respective dose groups, we recently also have analyzed the data on a single patient level in more than 200 individuals. And with this waterfall plot here on the top left, you get a very good vision showing that varoglutamstat treatment decreases pECCL2 in majority of participants here in purple, while most of the participants on placebo here in orange, show increased pECCL2 levels, all depicted in the algorithmic scale here as a change from baseline. And below, you see the correlation with a clear improvement in eGFR in the vast majority of patients on varoglutamstat, where the purple varoglutamstat bars show increased eGFR levels compared to the orange placebo bars showing decreased levels. And the right panel of the slide shows a statistically significant correlation between change in pECCL2 level in serum at week 48 and the individual slopes in eGFR over time in a scatter plot that's typically used for such correlations. This might look a bit complicated, but what you should focus on is that most of the purple circles are in the upper left quadrant, while most of the orange ones are in the lower right quadrant. The so-called Spearman's coefficient calculated from this reveals a medium inverse correlation, meaning that also statistically the reduced levels of inflammatory pECCL2 correlate well with the decrease in eGFR kidney function. This is also telling us that the majority of participants treated with varoglutamstat has a positive eGFR score, i.e., increased eGFR above 0, again, corporating earlier findings. So in summary, we show here very clearly that improvement of eGFR correlates with reduction of pECCL2, not only if measured in dose groups, but also on the individual patient level. Now I would like to shift gears and turn to recent data from our preclinical models. As a reminder, we have previously shown a beneficial effect of varoglutamstat on inflammation, fibrosis and kidney function in the ADI-CKD mouse model. We are now very pleased to report that we can incorporate these findings in an established model specific for diabetic kidney disease, the reninAAV-DKD model. I should mention that this is a very harsh model using diabetic mice with an increased induced hypertension and only one kidney left. Now based on this MOA, varoglutamstat does not directly address diabetes or hypertension, 2 of the important risk factors of the CKD/DKD reflected in this mouse model. But at the same time, you can clearly see here that QPCT/L inhibition with varoglutamstat resulted in a very impressive statistically significant reduction in inflammation as measured here by CD11c, fibrosis as measured by the glomerulosclerosis index and the kidney biomarker, plasma creatinine supporting an improvement in kidney function. So seeing the effects in the severely impaired mice is another confirmation for the potential of our approach and underlying our prior findings in the ADI-CKD model. These are highly encouraging preclinical results in a model specific for our initial target disease, diabetic kidney disease. In addition to diabetic kidney disease, we are investigating further opportunities for our kidney function improving approach. And together with our collaboration partner, the University Hospital in Hamburg-Eppendorf, Professor Tobias Huber's team, we have been looking into kidney-specific cells called podocytes in Fabry disease. Now Fabry disease is an X-linked genetic lysosomal storage disorder affecting more than 1 in 15,000 people. It is a rare disease which affects all ethnicities and is also recognized as being heavily underdiagnosed. This is characterized by deficiency of a specific enzyme, which leads to an accumulation of certain metabolic products, which in turn triggers a cellular stress response, including generation of reactive oxygen species or ROS in target kidney cells, the podocytes. This in turn resulted in multi-organ dysfunction and chronic inflammation that particularly affects the cardiovascular and renal systems. Disease-modifying treatments such as enzyme replacement therapy and oral capperone therapy have limited efficacy, particularly in advanced disease, which means that there's a significant need for new innovative therapeutic approaches. The current life expectancy for affected people even with the current treatment is 50 to 60 years. Now our partners at UKE have investigated Fabry podocytes and specifically, they have looked at ROS levels, which are indicator for chronic inflammation. We have just received preliminary data for the effects induced by varoglutamstat and VBY-2149 in this model. And here on the right, you see for both compounds a significant and dose-dependent reduction in the ROS levels as opposed to untreated cells. Again, these are very preliminary data, but we are seeking for confirmation shortly from an additional assay using a technology that directly measures the oxygen consumptions of the cellular level. These are very promising results, and we will help -- and they will help us and our partner to design follow-on experiments towards additional therapeutic applications for our glutaminyl cyclase inhibitors in rare diseases. And with that, I'd like to hand over to Frank for the strategic summary and outlook. Frank?
Frank Weber: Thank you, Mick. Thank you, Julia and Anne. There's no doubt that there is a high medical need for therapies that can improve or cure kidney function in a majority of patients. And with varoglutamstat, we have an excellent opportunity to become a unique, convenient new oral therapy for these patients with a high medical need and to transform the trajectory of currently always progressing kidney disease to a stable situation. The opportunity is accompanied by an impressive product profile. We have already compiled. Varoglutamstat is a first-in-class single agent that has shown already to stabilize and partially recover the kidney function. And it is already at that stage, we are a highly derisked development asset. Why is it derisked? Because, first of all, there is a clear development path to the market in diabetic kidney disease. There is no risk on the endpoints. There's a clear regulatory pathway, which we can follow. The second derisking is product specific. We have statistically significant and clinically meaningful data already on eGFR, which is the primary regulatory endpoint for approval. We have observed that effect independently in 2 studies, and we have done our homework by identifying the most promising subgroup that is patients with diabetic kidney disease, which -- a larger effect size than seen in other subjects. We have already established an excellent safety profile with treatment duration over across 2 years. And we have also seen synergistic effects on top of the standard of care in diabetic kidney disease, SGLT-2 inhibitors in a mouse model. Further on, we promised previously that we work on rare diseases, rare kidney diseases. And Mick just has presented the first very promising data in Fabry disease, which opens new opportunities both for varoglutamstat, but also for the follow-up compound. Then where are we today? We have already a compelling body of evidence. We have an innovative compound. We have a unique asset, and we have consistent data. In summary, we are a mid-stage clinical company with a strong proof of concept that varoglutamstat improves kidney function. And we have the mechanism identified and we dig deeper, further and we will continued on scientific excellence as shown, Mick with the new data. And the data we see in the preclinical assays and experiments are very consistent with what we see in the clinic. So we have a strong translational evidence level. The only limitation we see today is that the clinical data are generated in subjects with Alzheimer's disease, which have not been preselected for their kidney disease. And therefore, for an advanced kidney disease, we have not yet robust data. And this is why we are planning the upcoming milestone, and that is designing a Phase IIb study to confirm the effect in those advanced DKD patients, which are prospectively selected. That study is efficient and relatively short. And within 24 months after initiation, we should have the top line data for that study. Now how do we get there? There is 2 opportunities and options to move forward with that study. One is financing and one is partnership because the new study, of course, requires funds, which we don't have yet. We are actively pursuing both pathways, financing and partnership in parallel. We have received significant interest from pharma companies, and we are under CDA with BD activities ongoing. The opportunity is good and the quality of the data and the results are well received and confirmed by independent reviews and analysis. And we get, of course, important input by pharma companies on the next step of deliverables for the next study. Ideally, for a partnership, we would present the data of a future Phase IIb study to engage in a final collaboration. So where are we today? We have final steps to select the CRO for planned Phase IIb DKD studies. We are minimizing the time and cost to the actual start of the study once we have secured financing, and we are discussing protocols with kidney experts to ensure the best outcome. We have also secured the study medication supply for that study. So we are one step before the next milestone. And now we are looking forward that we can complete and initiate that program in the upcoming future. Thank you for your attention, and we're open for Q&A.
Operator: [Operator Instructions] Now we're going to take our first question, and it comes from the line of Sushila Hernandez from Van Lanschot Kempen.
Unknown Analyst: This is Meredith for Sushila. My first question is on the planned Phase IIb in diabetic kidney disease, how are your protocol discussions progressing with the experts? My second question is about, could you provide an update on how your partnership discussions are progressing? Has the mechanisms of action in kidney disease been a key topic given the additional analysis you have conducted? My third question, have you entered late-stage preclinical development with VY2149? And my last question, could you remind us by how much you would extend your cash runway if you draw under the SEPA? And do you currently meet the criteria to initiate these tranches?
Frank Weber: I'll start with the last one, and then you may need to remind me on the others because a lot of questions. So the first is the SEPA. We have no intention currently to -- in the near future to activate the SEPA. That's what I can say. That there is no plans on the table. Therefore, theoretically, the framework would allow us to engage for EUR 15 million over 3 years, but there is no step taken and no decision taking to start that in the immediate future. So then -- that I can tell you. Then on the follow-up compounds, we are -- you see that we are working deeper and further and continue to work on scientific excellence. That is, I think, a prerequisite to be successful in any science and any drug development, but we have not completed the nonclinical program. Also, this requires additional funding because the regulatory part of the nonclinical program is probably quite expensive and will be -- have a low single-digit million number or mid-single-digit million number, which we would need to identify in order to advance that program. Then the partnership discussions, I think we have been very specific and we made a slide on it. I think it's not wise to go deeper and further because we don't want to disclose to the companies we are talking to our strategy and how many and whatever that is not by a situation. So we keep -- we don't say more than we have said, but I think it's clear we are talking about it. We're looking at the best shareholder interest to see what is possible and reasonable at that stage. And this is what we're doing, and there is interest. There's no question that there is interest. Then the protocol discussion, and that is a little bit more a story we can talk about because depending on which expert you talk about, you get very different advice. And there are people who say, look, you're a new standard of care in diabetic kidney disease, do an all-comer study. So just except everybody with Stage IIIb IV, don't make the criteria too narrow because the data you have provided this is just a new standard of care and don't care about what the patient else get. And there's people who say you should bring a little bit more order in your patient criteria and at least stratify them according to what they get as a baseline therapy because your effect may be different and too much heterogeneity may affect your statistical power. So there is a little bit of discussion how people see the data. what we can generally say there is excitement about the data, and there is a big willingness to continue and participate in the study. And then I don't know what else did you ask? I think I missed one question, I think, maybe.
Unknown Analyst: I think about have you entered late-stage preclinical development with the VY2149 drug?
Frank Weber: What I said is we have not completed the preclinical package because we would require some funding additionally to this, which we are currently identifying. So -- and also, I have to say we have not spent and dedicated resources on it yet because we were waiting for the first orphan disease data, because we're considering that the follow-up compound may be particularly suitable for orphan diseases. And we needed the first data, which were presented today in Fabry disease. So we are encouraged by this, and this is probably giving an additional push for the follow-up compound.
Operator: [Operator Instructions] The question comes from the line of Joseph Hedden from Rx Securities.
Joseph Hedden: One on the pECCL2 data that you presented today. Just interested, would you expect to see a reduced pECCL2 with other DK drugs that are slowing -- DKD drugs that are slowing decline on eGFR? Or is this specific to varoglutamstat?
Frank Weber: Well, I think there is no evidence that any other DKD drug would reduce pyroglu-CCL2 because that is very specific for a glutaminyl cyclase inhibitor. The pyroglu formation of CCL2 is something with 80% to 95%, 99% done by the enzyme. There can be spontaneous dosing, but they won't be influenced by others either. As you know, there has been futile attempts to reduce CCL2 itself and not pyroglu-CCL2 by other companies in the past. We don't think that CCL2 is a valid target in kidney disease. You need to address the pyroglu version of CCL2 in order to get a result. And that I think Mick showed in a clear correlation, that correlation we don't see with CCL2. So first of all, to make it very clear, there is no evidence that any other drug would reduce pyroglu-CCL2. Secondly they may or may not effect CCL2. In the past there have been developer programs but from our point of view, that makes no sense at all because changing CCL2 does not change the disease trajectory in kidney disease, which is already confirmed by other programs, which didn't deliver results, but also from our data. So I think we are in a particularly unique situation. Of course, science has to learn it. Pyroglutamization is a form of protein maturation or protein modifications are not the standard of science yet in everybody's lab, but people have to learn that these maturations have a very important effect on how these peptides work and how active they are and what cascades they trigger and whatnot. And there are a big difference between CCL2 and pyroglu-CCL2. So that's probably what I can say.
Joseph Hedden: Okay. And then on your ERA Congress presentations, can you just give any color, did you get any feedback that you can incorporate into your future plans? Or did it lead to an uptick in interest in your BD discussions or any investor -- increased investor interest?
Frank Weber: Yes, I can confirm everything, and we have one of the parties showing up there. We have -- it is one of those, which we have continuous discussions under CDA. And I think it is important to present the data. And I think it is -- it gives additional stimulus and it clearly shows the evidence and it's a validation of the data. I think it was a very successful congress for us.
Operator: [Operator Instructions] There are no further questions for today. I would now like to hand the conference over to your speaker, Julia Neugebauer, for any closing remarks.
Julia Neugebauer: Thank you all very much for joining. We really appreciate your ongoing interest and support. We've shown clear progress, and there is a growing momentum in the kidney disease space. So we are firmly focused on advancing to the next stage of our growth journey. Thank you very much, and goodbye.
