Vivoryon Therapeutics N.V. (VVY) Earnings Call Transcript & Summary

Good day, and thank you for standing by. Welcome to the Vivoryon Therapeutics 2024 Third Quarter Earnings Call. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to turn the conference over to your speaker, Anne Doering. Please go ahead.

Thank you, Ralph. Good afternoon, and thank you for joining us today to discuss the company's third quarter 2024 results and operational update. This morning, Vivoryon issued a press release reporting its 9 months 2024 financial results and also provide an update on our progress, which was marked by compelling kidney function data as well as execution of important steps in implementing our strategy to advance varoglutamstat and kidney disease. This press release is posted on Vivoryon's website at www.vivoryon.com. On the call with me today are Vivoryon's Chief Executive Officer, Frank Weber; our Chief Business Officer, Michael Schaeffer is also available for Q&A. We will begin today's call with opening remarks from myself, giving you an overview of the key highlights from the third quarter and post period update, after which we will move to Frank, who will provide some details on the exciting news update we announced yesterday, which is the positive kidney function data from our VIVA-MIND Phase II study. I will then review the financial results for the third quarter of 2024 and conclude the call with an overview of our corporate outlook and strategic update. Following the prepared remarks, we will host a Q&A session. 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 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 condition, 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. For those that have been following Vivoryon over the last month, you know this has been a period of major change for the company. Since March of this year, we have step by step rolled out a strategic shift to kidney disease and in particular, have presented to you the results from 2 Phase II studies demonstrating varoglutamstat's potential to beneficially impact kidney function, which provide the foundation for this new path forward. Now shifting to the third quarter and post period update. Clearly, the biggest development is, of course, the top line VIVA-MIND data we disclosed yesterday, which shows a highly significant improvement of eGFR versus placebo confirming VIVIAD eGFR results and providing a second Phase II long-term data set. Frank will walk you through these data in detail shortly and show you why we can confidently say now that with the strong data package generated to date for varoglutamstat in kidney, we have a unique chance to become a key part of the treatment landscape for a number of diseases with high unmet medical needs. Another important development in the third quarter was our presentation at ASN. We were thrilled that kidney outcome results from our VIVIAD Phase II study were selected for a late-breaking oral presentation at ASN Kidney Week, which is the world's premier nephrology meeting. Frank's presentation was very well received, and we have been extremely encouraged by the positive reactions we received from the community. Vivoryon hosted a virtual kidney disease KOL event in September, during which the experts provided insights into the limitations of current standard of care and new developments in kidney disease. They outlined that novel medicines are needed with MoAs suitable to addressing the kidney -- the key inflammatory and fibrotic pathways underlying this disease and the potential of varoglutamstat in this space. So as you can see, once again, we've had a very active reporting period marked by continued strong progress in advancing varoglutamstat for kidney disease and are poised to enter 2025 with positive momentum. With that, I will now turn the call over to Frank.

Thank you, Anne. Dear, ladies and gentlemen, good morning, good afternoon. We're going to move to the mechanism of action and the groundbreaking discovery we announced recently that actually with the QPCTL or the isoQC as the enzyme, which is responsible for reducing kidney inflammation and fibrosis, and that improves kidney function. And as a short recap, the pro-inflammatory and pro-fibrotic peptides require largely pyroglutamization that is a ring form at the end terminal and of these peptides to become fully functional and potent. And varoglutamstat is an inhibitor of that enzyme. And therefore, the pyroglutamate peptides do not occur with same amount and are significantly reduced. And there are various numbers of peptides, which are involved in the inflammation, fibrotic cascade and then end up creating kidney dysfunction, kidney fibrosis and kidney insufficiencies. And we have, in that slide, you can see below run and published animal experiments and pharmacology experiments, which show that we reduce the markers of inflammation, including pyroGlu-CCL2, IFN-gamma and TNF-alpha. We can show that we reduced Collagen 3, alpha-SMA and CX3CL1, which are fibrotic markers. And then we can show that we improved eGFR and reduce urea and Cystatin C in this pharmacological models. And based on this novel and groundbreaking discovery and mechanism, we now go to the VIVA-MIND U.S. study design and see how that mechanism impacted on that U.S. study. The U.S. study was an NIH-sponsored study for early AD and was a 1:1 randomization of patients between varoglutamstat and placebo. And there were -- those funding elements included in that study in the sense that if the 600-milligram would not have been well tolerated in the DSMB interim analysis, then we would have dropped to 300 and 150-milligram. But we announced already about a year ago that the 600-milligram BID was well tolerated and can continue and therefore, not dose de-escalation to 300-milligram was needed or required. And second quarter 2024, we decided together with the ADCS to terminate that study because we saw in VIVIAD no efficacy in early Alzheimer's disease, and we did not deem it appropriate to continue a study in a nearly identical population with the same dose, just with different endpoints in this population. And therefore, we have about 109 patients now allocated to placebo and to active instead of the finally planned 414 and 180 were planned to formal interim analysis. So there were much less patient. But that is quite important because we can see that with this little patient, we have highly significant eGFR patients. Just to remind you what that patients were. These were patients selected for early AD with an MMSE of 20 to 30 and a CDR sum of boxes between -- either 0.5 or 1 and an age of 50 to 89 years old. And we had objectives to look at the safety and tolerability as well as efficacy for Alzheimer's disease and the primary endpoint was CDR sum of boxes, and that was different than the VIVIAD study, where we had CogState NTB. And then we had an interim preplanned analysis after 180 patients were treated for up to 24 weeks to look at interim efficacy using EEG and a neuropsychological test battery. Kidney functions were prospectively defined eGFR being a safety parameter and we did not change that because we didn't deemed it appropriate after we saw the VIVIAD data to do a last-minute post-hoc evaluation to efficacy. We thought that is a kind of cheating. Therefore, we left it as a safety prospective parameter. And as such, it is reported here. So going on, I just want to remind you that the top line data as always, are preliminary and may be subject to minor changes on additional analysis and quality check, which you always have. And so that should not change the overall allocation of data, but there can be some numbers changing, of course, always to happen until we have final, final data. Going to the next chart. This is the distribution of patients between active and placebo. And it starts, unfortunately, with a little bit of a confusion because we have 53 patients and 59 patients in -- actually it should be 58 and 52 and 57, and that is due to a patient, which was initially randomized to placebo, but got 1 single dose of varoglutamstat, which was an error and administration error by the site. But that, of course, made the patient still in the efficacy group in efficacy in placebo. But for safety, you needed to put him into the varoglutamstat group, because he has exposure to the drug. That should not change any interpretation of the results, just a small detail. So you see that the groups were well equilibrated regarding sex and age. The average treatment duration is probably quite important is 45 weeks. In the study, the CDR sum of boxes at baseline was 3.35 and 2.99. So in the early stages, the eGFR was around 77 for both groups. Then you see how the study rolled out, as it was planned to have evaluated by the 72 weeks in it, if it would not be prematurely terminated. We had only 25% to 33% completing the 72 weeks and the rest of the patients were either prematurely terminated by the sponsors, that is our decision to stop the study or by withdrawal of the subject or all other together. So we look here at data, which are, of course, much shorter and much smaller than in VIVIAD. Next slide, please. So we, first of all, want to discuss the results on Alzheimer's disease. And at the pre-specified primary, key secondary and relevant endpoint of ADAS-Cog, we saw no clinically meaningful and not statistically significant differences between varoglutamstat BID and placebo. And I want to remind you that the additional data will come, EEG, biomarker data in the CSF and in the blood, but they will only be available in the first quarter 2025. In that respect, VIVA-MIND fully replicates the finding in VIVIAD, where we had the same outcome for Alzheimer's disease. So on the right side, you probably find some specificities of which I have already talked about. So we can jump to the next slide, which is safety. And we see in VIVA-MIND, a very good safety and tolerability profile. We did not see any additional safety. And here it is important that VIVA-MIND exclusively used an accelerated fast titration regime starting at 150 milligrams and go to 300 and 600 milligrams, whereas VIVIAD started at 50-milligram and it took a lot of time to come to 600 milligrams. So it is a more convenient and accelerated regime we tested here but it did not impact negatively on safety. Actually, the safety arm quited equilibrated with a similar number of related treatment adverse events in both groups. Also by severity, there are no major differences, also the serious and the related serious treatment emergent -- adverse event didn't show any difference. And there is -- also for patients this drug modification has no difference. And for drug discontinuation, there is a minor difference, but not a lot. I want to remember or tell you that there were 2 patients dying, which were unrelated to the drug in the study, one because of the gastrointestinal bleeding and the surgery for this and the complication of the surgery thereafter, which happened many weeks after stopping of treatment and the second patient having a fall down the stairs and having a patient provision not to have intensive reanimation done and therefore, was dying thereafter. Then we come now on the next slide to the kidney data. And we see here on the left side, the difference between placebo and active for the totality of all patients and all visits. So what we did here is we simply took all the data around the treatment and substracted active and placebo. And that is the difference between it. So you see it's a little bit about 4-milliliter average difference across all visits and each visit active is better than placebo. And that is highly significant, as you see with the p-value. And as said, that is all patients all visits. So there's no subgroups, no division, no post hoc here, that is the totality of the data. And then you look on the right side, where we divided the efficacy parameter in 2 periods, one in the starting period, where the drug was titrated and a little afterwards of the titration that is between week 4 and 16. And you see that the effect size of this placebo is already significant, but with around 3-milliliter or 3.3-milliter, of course, much smaller than later between weeks 24 and 72, where you basically reach a plateau of efficacy of above 5-milliliter difference in -- of active placebo. What it means is that each of these visits, the average of the active was more than 5-milliliter better than the average of placebo. And that's, of course, a huge effect size, which is 3 to 4x higher than everything you saw with improved drugs used for the treatment of kidney diseases these days. Next slide, We want to dive a little bit in the sustainability and here on this slide, sorry. This is, first of all, the slide where we compare 2 calculations, as we did in VIVIAD. So we look MDRD and CKD-EPI. And while there is a little bit of difference, the significance level and the effect size is very comparable. It's just a different formula to make sure that we are not facing only one thing and forget another one. You see that this data is robust, comparable and consistent. Next, now going to the comparison of VIVIAD and VIVA-MIND because in the following charts, I want to present you a little bit more about the consistency between the VIVIAD and the VIVA-MIND study. So first, before we go into the data, we need to understand that the studies have similarity and differences. So the study completion, of course, VIVA-MIND is a smaller data set as a discontinued study and VIVIAD is a completed study as per protocol. The mean age is quite comparable in VIVA-MIND, but a little bit older than in VIVIAD. And we saw that the upper age range in VIVA-MIND was 89, whereas in VIVIAD, it was 80. So that is explained. The number of patients treated, as I said, is smaller in VIVA-MIND and VIVIAD by 2.5-fold actually. In VIVA-MIND, we only tested 600 milligrams as explained because we did not need to down escalate the study, whereas in VIVIAD, we tested up from 300 and 600 milligrams and then besides these that we decided that 600 milligrams is good, and we moved everybody to 600 milligrams. The dose escalation is different. So in VIVA-MIND, we started fast with 150-milligram BID, and we reached 600-milligram at week 9, whereas in VIVIAD, we started slow with 50-milligram, and we reached to 600-milligram at week 13, so 4 weeks later. Mean treatment duration was also shorter in VIVA-MIND than in VIVIAD, 46 and 76 weeks or you can put it in other words. The longest treatment duration in VIVA-MIND with 72 weeks is still 4 weeks shorter than the average in VIVIAD. So we have a shorter treatment set. And based on this result -- based on these facts, the results are actually, I think, mind-blowing in terms of the robustness and consistency. The number of patients with eGFR results at week 36 and later was 73 -- sorry, 73 in VIVA-MIND and 246 in VIVIAD. So about 1/3 with long-term data. Next chart. And when you now compare what the results are between VIVA-MIND and VIVIAD and your compare comparable patients, meaning only patients treated with 600-milligram at -- in VIVIAD, and of course, all in VIVA-MIND, you see that numerically, there is even a slight advantage for VIVA-MIND. But overall, it's pretty consistent around 5 or above 5 milliter average benefit in the period, where you have a stable dose range. So this is 24 to 72, respective 36 to 96, and it's adjusted to the slower treatment titration period in VIVA-MIND. So what you see is -- sorry in VIVIAD. So what you see is the data are when you compare apples with apples, so the same dose and a comparable period post full dose, you see exactly the same results, and that is an average of 5 milliliter for each visit in each patient better on active than placebo. Going and is, of course, significant in both studies and similarly significant. Next, and here is what I announced before. We look at week 60s and 72s, because what is important not only is to see the effect size, but also whether this effect size is sustained across the whole study. So on the left part of the chart, you see the week 60 results. That means, we compare here the effect size observed only at that single visit. And you see in VIVA-MIND, we had about 5.5-milliliter. And in VIVIAD, we had about 4.5-milliliter. And of course, in VIVA-MIND, we have much less patient at that time point than in VIVIAD. And of course, here, we also only compare the 600 milligrams. And on the right side, you have the 72 weeks, which -- results, which are the last visits in the VIVA-MIND study, but it's not the last visit in the VIVIAD study because you know VIVIAD went up to week 96. But we compared week 72 in both studies just to see how the effect is sustained in VIVA-MIND and VIVIAD. And what you see is despite only having 13 and 20 patients in VIVA-MIND at that time point, we have a p-value of 0.002 and an effect size at that visit day of more than 6-milliliter difference between active and placebo. And in VIVIAD, the data were correspondingly a little bit above 5-milliliter and also statistically significant. So what we can conclude from that analysis that in both studies, the effect size was sustained in the midst of the second year. Until the end of the second year, there was no lowering or reducing of the efficacy over time. The efficacy was fully maintained and that was significant until the last visit. Next chart. I want to summarize the findings of our Phase II program in this chart. We now have 2 double-blind placebo-controlled studies, one collected in Western Europe and one in U.S., totally different investigation sites, totally different CROs, not connected to each other and both show a consistent, very comparable statistically significant and clinically meaningful improvement of eGFR for varoglutamstat versus placebo. In both studies, eGFR was improved above baseline and stabilized across the whole treatment period for up to 96 and 72 weeks, respectively. These results provide a robust, and I want to send a very robust evidence of the treatment benefits. We have good safety results in VIVA-MIND with the accelerated dose escalation scheme and that provides a very good pathway for a convenient and commercially viable dosing schedule. And what is also important looking forward is that VIVA-MIND with this small patient number of 109 patients, of course, support the sample size planning of 120 patients or less for the next planned study in diabetic kidney disease, which we announced before. And so the sample size assessment we did before, I think, was very solid and probably we need a couple of less patients, but we will follow up on this in a later conference when we have fully digested the VIVA-MIND data. So we will continue to analyze the data. We're here at top line only data, first to view on it. And with that, I want to hand over back to Anne.

Thanks, Frank. Let me take you through the key figures for the period. R&D expenses in the first 9 months of 2024 amounted to EUR 12.6 million versus EUR 10.4 million in the same period of 2023. This increase of EUR 2.2 million was largely attributable to the increase in clinical costs from the VIVIAD and VIVA-MIND studies as well as investments into kidney-related research and analysis. We have seen a decrease in G&A expenses with costs of EUR 4.9 million in the first 9 months of 2024 compared to EUR 6.8 million in the first 9 months of 2023. This EUR 1.9 million decrease was largely attributable to higher compensation of nonexecutive Board members in 2023. All of this resulted in a net loss for the first 9 months of 2024 of EUR 17.4 million, the same amount as we had in the first 9 months of 2023. The company held EUR 12.5 million in cash and cash equivalents as of September 30, 2024, compared to EUR 28.6 million, which includes cash and cash equivalents and term deposits within financial assets as of December 31, 2023. Cash utilization for the first 9 months of 2024 reflects the intensive investment period in VIVIAD and VIVA-MIND, especially in the first 6 months of the year, both of which are expected to continue to ramp down in the months ahead as those studies conclude. Our reduction in cash and cash equivalents for the third quarter was less than half seen in each of the first and second quarter. We updated our financial guidance and expect our cash and cash equivalents being sufficient to fund our operating plan into the third quarter of 2025. Looking ahead into the upcoming months, we will continue to thoroughly analyze the VIVA-MIND data and expect to disclose additional results, including biomarker data related to varoglutamstat, unique MoA as well as preclinical data on orphan kidney diseases from our scientific collaboration. In 2025, Vivoryon plans to start a Phase II study in DKD, which we have outlined previously and see as the next natural step given the strong VIVIAD and VIVA-MIND data. Depending on anticipated preclinical results from our collaboration with Professor Huber, Director of the III Department of Medicine, UKE, Hamburg, Eppendorf. We are also looking into potentially launching a small orphan disease study. As a reminder, all potential future clinical studies are subject to additional funding and our partnership, which we continue to actively explore. Beyond 2025, we anticipate upcoming meaningful milestones to include interim and full data readouts from the planned DKD Phase III study, which we have also outlined previously in detail. So as you can see, we have lots in store for 2025 and beyond that will build on our current momentum. I'd like to conclude by reiterating that despite the setback in AD earlier this year, we have been able to successfully generate compelling efficacy and safety data and people at risk of kidney disease from 2 independent double-blinded placebo-controlled Phase II study, and we are now very well set up to become a key part of the treatment landscape for a number of diseases affecting the kidney with high unmet medical need. Backed by our strong scientific foundation, varoglutamstat's novel mechanism of action and confirmed target engagement, the extensive safety data package with convenient dose escalation scheme as well as compelling dose-dependent long-term kidney function improvement, we have a focused development plan in place. Furthermore, based on new filings, we anticipate composition of matter patent protection to be extended to beyond 2044. In addition, we have been active in strengthening our patent protection in the kidney field in general. We actively pursue -- pursuing funding and BD opportunities to realize the full potential of the significant commercial opportunity to DKD and beyond. With that, we will now open the call to take questions.

[Operator Instructions] We are now going to proceed with our first question. The questions come from the line of Natalya Davies from Intron Health.

Congratulations on the encouraging data. Just a couple for me. Firstly, can we expect any additional subgroup analysis from the VIVA-MIND study or any additional data on transaminase levels or weight loss, diastolic blood pressure? And any of those would be great. And yes, any further analysis that we can expect on both of the trials. And then the second question is just on the kidney opportunities outside of diabetic kidney disease such as Fabry disease. Has the preclinical analysis started? Or is this subject to additional funding?

Yes. So first of all, we are -- as you said, we are at the beginning of the analysis of VIVA-MIND. We are happy that VIVA-MIND is consistent with VIVIAD. But of course, we are not through all the analysis of VIVA-MIND. We are just started with it. So we will take our Christmas holidays and dig into the data and come up with all the things you have asked for. And yes, of course, that will be then published as said and disclosed at the next webcast and press release. And the same is true for diabetic kidney disease. We were convinced that this is a very good indication based on VIVIAD. We still need to do some analysis in VIVA-MIND, but there are not so many patients with diabetes in VIVA-MIND. So let's see what that brings. But given the overall results are positive, I expect that similar things would happen for diabetes patients. But I haven't seen the data personally, so I cannot make any promises to be very clear. But we are looking forward to looking -- to dig deep into the data and come back to you with all the results we will have. Did I answer your question? Or is that not what you asked for?

Sorry. And just on the opportunities outside of diabetic kidney disease, are there any updates on that front?

Well currently, no. We have no yet the updates on the orphans and other indications, but we will work on this, and we will come relatively short in this. These are partially academic collaboration, but not necessarily run by the week, probably more by the month. And so we are ourselves waiting for that. I don't know any update material on this, but it will come.

We are now going to proceed with our next question. The questions come from the line of Lucy Codrington from Jefferies.

So just following on from that, you mentioned that there was a small proportion of patients with diabetic kidney disease in this study. Can you tell us how many, if any, patients did have diabetic kidney disease across the 2 arms? And then just related to that, any of the patients, are they on concomitant SGLT2 or GLP-1s, both within VIVA-MIND and in the VIVIAD study? And then just on the final comment or a comment towards the end about extending the composition of matter IP. Just what's driving confidence that, that will be feasible for varoglutamstat?

You want to start, Mick, with the IP?

I can -- Lucy, that's Michael. I can start with the IP. Yes, I mean it's probably always not straightforward to say in an IP process. But what I can tell you is that, I mean, if you ask about our level of confidence, it's pretty high that we have a good chance here to get the patents we have filed also granted. So I also want to note that actually in the whole field of QC inhibitors, all the patents we have filed, they did grant us in the past, and we have no intention that this will change.

Yes. Maybe I can add to this. We are -- I mean, filing a patent to get it approved is a process. That process run as by the books. And we will have some updates in the future on this once there is the time to update you on this. It's probably not so far away. So of course, until that point is happening, we cannot give you any information, but we are in the process as it should be. And there are no bad surprises so far. As you know, we are patenting the compound we're using under specific contingency, I would say. And there was a genius move from the past. And I think we let it there until we can fully speak about it in the public. And regarding diabetes patients, I mean, the process we do is that we, by hand, check the identification of diabetes and prediabetes patients, and we are currently trying to understand what is the prediabetic patients, so some with disturbed hypoglycemia or hypoglycemia and disturbed glucose tolerance versus the full diabetic patients. We expect the number of full diabetic patients to be something between 10 and 20. But that separation is currently ongoing to really identify the group's properly and to ring-fence the number. So I cannot give you a more precise number because while a patient may have a history of diabetes or impaired glucose tolerance that needs to be checked with the laboratory data and the concomitant medication and the history accurately. And we have top line data now. So we are, from a timing perspective, not fully through this, so I cannot give you more precise information on this. And of course, we will disclose the concomitant medication, but the patients who had diabetes dose, had the typical co-medications, including some patients with SGLT2s. How many they are? I have to wait until the data are fully mature in QC. Did that answer Lucy? Was that....

Yes, I think so.

We are now going to proceed with our next question. The questions come from the line of Joseph Hedden from Rx Securities.

Congrats on this positive consistent data. Just on the plan for the Phase II DKD study, the fact that you've seen that these data are quite consistent with VIVA-MIND, VIVIAD, does that change the plan in any way, the recruitment size or any age factors of that study? And then secondly, on the cash runway and the streamlining that you've been doing to extend it, has that affected any of the preclinical work that you're doing? Is there anything there that's now not being explored that was previously part of the program?

So we actually did more in kidney than we ever planned. But of course, there are limitations because as you can imagine, the opportunities are infinitive to do exploratory pharmacology in animals or in cells, you could do thousands of things, but that we have neither the manpower nor the money to do everything, but all the clinical activities have been started and we haven't restricted the evidence generation in nonclinical based on our financial situation. Of course, we are careful with our spending, but that doesn't mean that in that area, we would have restricted. What we have restricted is investments in Alzheimer's disease, clearly, because currently, we have with these results and VIVA-MIND confirmed with the current dosing regimen, no way forward for Alzheimer's disease. Now we are looking, of course, the alternative options, but the mainstream is diabetic kidney disease and the experiments for kidney disorders are fully run. That's one thing. The other thing of the sample size. As I've announced, we have not recalculated the sample size based on the VIVA-MIND results and the consistency thereof. And that is because the results are fresh from the press, and we could not make a statistical model, including VIVIAD and VIVA-MIND data. As you see they're totally homogeneous. There is no difference between the data. That, of course, will facilitate or no meaningful difference between the data. Of course, there's minor differences. Sorry, I have to correct this, but there's no meaningful difference between the data. So that helps, of course, planning the next study and probably will more reduce the sample size needed. But on the other hand, we don't want to do a totally minimalistic study. That means our aim is not to invest as little money as possible, because we want to have a meaningful study and robust data at the end. So we -- a too small study may not be convincing either even from a statistical point of view, it would be the feasible, but I would not recommend to go down to a minimum. So we try to find that good balance between evidence generation and statistical sample size. And I think we are in a good spot to assume that 120 patients are the max, max, max and likely it will go more down. But if it's too small, then of course, everybody scratches their head, even have a p-value of the relevance of this. So that's a little bit between the 2, where we are trying to find a solution in upcoming weeks. And then, of course, the final product will have to go again through the KOLs. And need to be tested and then we're going to publish it and discuss it with you.

[Operator Instructions] We are now going to proceed with our next question. The questions come from the line of Luisa Morgado from Van Lanschot Kempen.

First of all, of course, congrats on the data confirming your earlier findings. My first question, in terms of the VIVA-MIND study analysis, what are the main motives behind withdrawal by the subjects themselves? Yes, if you could elaborate on that.

This is an Alzheimer's study and it's done in the U.S. And you know that the distances from study sites to where the people live are meaningful. And if the patient the -- burden of the study is much higher than the patients thought initially or they have problems with the relatives taking care of them, patients drop out. The other part, which was a withdrawal reason is that lecanemab became commercial in the midst of the study, and we had a couple of patients who elected to leave the double blind placebo-controlled study, because they could be on placebo for 1.5 years and elected to go to commercially then available lecanemab, which was, at that time, approved. So we had a couple of those, and that explains a little bit the number.

Okay. Clear. That's quite helpful. And in terms -- maybe a question more for Anne in terms of the expenses over the next quarters, what can we expect here? And when will the -- is the VIVA-MIND trial completely terminated altogether? Or when will that happen?

Luisa, as you've seen the progression of our sort of cash burn or cash usage over the entire year so far has gone progressively down. So we've had a lot of expenses in the first 6 months of the year related to VIVA-MIND and VIVIAD. And then you've seen a step down in the third quarter. And so as those studies do come to a conclusion, we should see that ramping down. And we've also had the additional update today of our guidance into the third quarter, and that also reflects that ramp down.

But probably to be a little bit more concrete, we haven't paid every single VIVA-MIND. There are still some remaining expenses coming also, because there are additional subgroup things and statistics and so on. So there will be some more expenses. But I think the vast majority, of course, of the costs have already been paid. So there are some things to come, but that -- largely Phase II program is paid, a little bit to come. And then we have some typical operational expenses of the company, plus some nonclinical activities for the kidney disorders. So that's probably it. But our confidence in financial planning and the team's financial capabilities is good. And this is why we made today the announcement that due to third quarter cash with what we have today is [ significant ].

[Operator Instructions] We have no further questions at this time. I will now hand back to you for any closing remarks.

Yes. First of all, I want to thank you for your attendance. And I want to close with the remarks that repetition and replication is the name of the game and consistency of data is very important to make scientific and medical judgment and look at the scientific merits of the data. I think we are largely through a transformation of the company from a hopeful Alzheimer's disease to a validated and confirmed kidney company with additional opportunities. So having seen that in very well-conducted, high-quality, robust and randomized placebo-controlled studies, which both are long term of 72, respectively 96 weeks, I think, gives us a very solid foundation for moving forward. And happy to have you on the next call and see how we are progressing. And with that, I wish you very happy Christmas period and good relaxation period, and see you back next year. Thank you.

This concludes today's conference call. Thank you all for participating. You may now disconnect your lines.