Please be advised that today's conference is being recorded. I would now like to hand the conference over to our speaker today, Anne Doering. Please go ahead.
Thank you, Nadia. Good afternoon, everyone, and thank you for joining us today to discuss the company's full year 2023 results and strategic updates conference call. This morning, Vivoryon issued a press release reporting its full year 2023 financial results, including a strategic update, which 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 program, 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 materially 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 you're at. 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. I will begin today's call with opening remarks, then Frank will speak about Vivoryon's clinical developments with varoglutamstat, our lead asset, where he will speak about Alzheimer's disease, and we also have exciting news in kidney disease that we want to share with you today. After Frank, I will then review the financial results for the full year 2023 as well as conclude the call with our outlook and strategic priorities. Following the prepared remarks, we will host a Q&A session.
Firstly, I would like to thank the team for 2023, a year with substantial advances which included showing meaningful progress across clinical studies as well as a successful capital raise, the expansion of our management team, and unveiling a growth strategy beyond Alzheimer's disease. Obviously, the events of the last months have overshadowed these achievements, so let me dive right into the most important post-period developments which have revealed an exciting new opportunity for varoglutamstat. In 2024 to date, we've encountered both challenges and opportunities following the announcement of the results from our VIVIAD study in March. Unfortunately, in line with the top-line results reported at that time, our subsequent analysis confirmed that VIVIAD did not meet its primary and secondary endpoints in early Alzheimer's disease.
In light of this outcome and in line with our commitment to prudent resource management and allocation, we have made the difficult decision to discontinue VIVA-MIND early and cease preparations for the VIVALONG study. These adjustments reflect our focus on prioritizing resources for initiatives with the highest potential for success. While the outcome of VIVIAD is disappointing, our thorough analysis revealed encouraging findings related to varoglutamstat's potential in improvement of kidney function. These findings provide strong evidence of the potential therapeutic application of varoglutamstat in kidney disease and opens a new and exciting avenue of clinical exploration, leveraging our learnings from prior data and utilizing the versatility of our investigational therapies. Additionally, in response to our evolving corporate outlook, we implemented changes to our management team. We believe these adjustments ensure alignment with our revised strategic priorities and better position us for future success.
As we move forward in 2024, our primary focus remains on unlocking the true value of varoglutamstat and our broader pipeline. We are committed to exploring the potential of varoglutamstat in kidney disease, marking a shift in strategic focus towards inflammatory and fibrotic disorders. At the same time, in early Alzheimer's disease, we intend to assess the potential of a higher dose of varoglutamstat. We will also continue to explore and develop QPCTL inhibitors in inflammatory and fibrotic diseases, leveraging our expertise in this area. While maintaining a focus on our lead candidate, we will also selectively assess early pipeline development opportunities. In order to support our growth and advance our pipeline, we will continue to actively pursue funding and business development opportunities that align with our strategic objectives. Our prudent cash runway management ensures financial sustainability, extending our cash runway into the second quarter of 2025.
With that, I will now turn the call over to Frank.
Thank you, Anne. Good morning, good afternoon for all who joined in and visited. First, we'll come up with a summary of the results which we have observed in the VIVIAD study and then go in quite a technical detail in Alzheimer's disease and kidney disease and summarize the findings. As an initial summary, the detailed analysis of VIVIAD, which we did very diligently and turned a lot of tables, listings, and figures around, does not suggest any consistent effect of the drug in doses up to 600 milligrams b.i.d., which we used as the top dose in VIVIAD in early Alzheimer's disease. At that dose, we found highly significant effects on improvement of kidney function.
These non-significant observations in early AD were across all primary and key secondary endpoints as well as across the majority of the exploratory endpoints, with two only exceptions, and that is a DSST or WAIS-IV test, which is a coding test, and the letter fluency test, which showed a significance in favor of the drug at week 48. From a safety perspective, the drug was very well tolerated. We had very low discontinuation rates due to adverse events, and we had no evidence of any symptomatic ARIA in the clinical setting. And in the conclusion, jumping a little bit ahead, is that we are looking at it that 600 mg b.i.d. lost the efficacy signal, which we saw in the SAPHIR study, at 800 mg b.i.d., and maybe we have been too low with the top dose in the VIVIAD study.
Therefore, we continue our assessment of potentially higher doses of varoglutamstat, higher than 600, probably going back to 800 or 900 in early AD. But these are currently only assessments. That doesn't mean we have started a study or we intend directly to study. We need to analyze the data in that respect first. Looking at the kidney function, we saw a statistically significant improvement of the kidney as measured by the estimated glomerular filtration rate, which is the key primary endpoint of all kidney outcome studies. We could measure it across two years. That is a very long period because VIVIAD went up to two years. That treatment effect was also sustained up to two years.
The effect size was stronger in patients with risk factors for kidney disease, so those who had diabetes type 2 and baseline or hypertension, than in patients which had no risk factors for kidney disease. That clearly supports the mechanism of action of QPCT inhibition in kidney disorders, and that shows that varoglutamstat is a viable molecule for inhibiting the glutaminyl cyclase . The mechanism is proven to be beneficial, and the molecule is proven to be viable, at least in the kidney disease. Going now to the detailed results of the VIVIAD study, and I first start in the section with Alzheimer's disease. There are a lot of numbers and p-values, which I will guide you through in the next charts.
I'm sorry for being very technical, but I thought it is important that we are very clear and open and transparent about what we observed, and everybody can look at the figures and make its own interpretation of it. So the next chart shows the key primary and secondary endpoints of cognition as bar charts. So what we did in the study is we developed a slope analysis across all measurement time points for all patients and all visits. And these slopes, of course, show a decline in cognitive function. And each of the boxes shows a different variance of the Cogstate neuropsychological test battery. The primary endpoint was the three-item construct, which is on the left side, on the left bar. In the middle, you saw the four-item construct, which is also called Cogstate battery and is an approved scale for measuring cognition.
Then you see the full cognitive test battery with 8 items on the right side. All these slopes show a decline of cognition, as you see, and this is a unit, 0.285, and nobody, of course, can say what it is and how important it is because the unit doesn't tell you this, but it is a clinically significant decline from baseline across 96 weeks. There is no difference between the pink and the yellow bar. The pink is the compound, and the yellow bar is the placebo. You see that the p-values for the comparison between the two treatment arms are for the primary endpoint, 0.81, for the key secondary, 4-item scale, 0.96, and for the 8-item scale, 0.77. You see there is, when you look at the effect size, no difference.
But what you can see and what we want to mention here is that the overall decline from baseline to end of study was always highly significant for all three endpoints. So there was progression in the patients from baseline to endpoint, so the scale itself is sensitive and meaningful and measures the progression of the disease. There was just no difference between varoglutamstat 600 milligrams twice daily and placebo. Going to the next chart, we see the two further key secondary endpoints, which were pre-specified in the statistical analysis plan. The first box on the left side shows you the Amsterdam scale of activities of daily living at week 48, and you see very similar pictures. Both arms declined throughout the study in a very similar way, with no statistical significance between the arms.
On the right side, you see the EEG, relative theta power, the one which was highly significant in SAPHIR. But here we see, again, no difference between the two treatment groups, and here a good result would be going down. A bad result is going up. So the theta power increased in both arms in a very comparable way. That concludes that the pre-specified primary and key secondary endpoints did not show, at a dose of 600 milligrams, a difference to placebo. Moving to the next chart, and this is a summary of all the pre-specified subgroup analyses we did in the statistical analysis plan, and we, of course, conducted these analyses, and here I summarize what the findings are.
We saw no clinically meaningful and no statistically significant differences between varoglutamstat, 300 milligrams or 600 milligrams, or both together, against placebo for stratifying patients by baseline severity according to the Mini-Mental scale; according to the stratification by the APOE4 status ; according to the stratification of phospho-tau in the CSF at baseline, so high versus low phospho-tau; no difference between patients who had already been treated for Alzheimer's disease with available, commercially available, and approved medications versus treatment naïve; and also by stratification of the functional impairment at baseline. Then we conducted an additional series of analyses for exploratory endpoints. That means other endpoints like different EEG endpoints, cognitive domains, and biomarker in the CSF, like phospho-tau, YKL-40, or neurogranin. There was, in none of those, a meaningful or statistical difference between active and placebo.
The only, as I mentioned, significant difference was for the DSST and the LFT at week 48, but the effect sizes were relatively small, and the effect was not sustained at the end of the treatment and not observed at week 24. So that was the summary of the Alzheimer's results in the VIVIAD study. Now I come to some, sorry, quite complicated consideration of pharmacokinetics and target occupancy. It becomes very technical here, and I apologize for this, but for some of you, it may be very important information to make an assessment of what we did. So the first message is we measured varoglutamstat concentration in the cerebrospinal fluid under treatment at week 48 in the VIVIAD study. And we measured the 300 and the 600 milligram dose. That is in the left chart, the pink and the orange colors.
You see that the median concentration in the CSF was 21 nanograms per milliliter or microgram per liter, and that's the same thing, and 68 microgram per liter at the median for the 600 milligram dose. What we plotted in green are the data from SAPHIR we had obtained at 800 milligrams. You see it was 115. You see that the difference between 300 and 600 is about the same as between 600 and 800, and that is because the drug has a little bit of accumulation at higher dose. So that is all expected, and we knew all this. When you look at the right side, you see the target occupancy of the drug in the CSF, so in the fluid of the brain. You see that the blue curve with the red dots is the PKPD model we developed in Phase I.
The little orange dots are the target occupancy values we observed in the VIVIAD study. The green dot is the target occupancy we observed in SAPHIR. You see that all these dots fit perfectly that line. They're exactly where they should be. So we can conclude that the VIVIAD study was perfectly conducted. There are no issues in formulation or drug availability or bioavailability. The drug went in the predicted way where it should go. The only observation you can see is that the target occupancy for the 800 milligram is very similar to the 600 milligram in the CSF, but the kinetic is very different.
Of course, that raises the question whether the CSF is the right place to look at target occupancy or whether we need to look more into the intracellular compartment in the brain, which is, of course, nearly impossible to measure in the clinical study because we cannot puncture brain cells in an Alzheimer's patient. Going to the safety data now. Here we see that what we summarized before, that the drug was very, very well tolerated. You see that the number of patients who discontinued treatment is comparable, specifically when you look at adverse events. The rate of adverse events is basically identical because there are, of course, more patients in the active arm than the placebo arm. When you look at percentages due to adverse events, you come to the same number.
You see the majority of patients actually withdraw from the study, usually because they lost their study partner or they were so more severe and advanced that they basically didn't want to come to the study site anymore because it was too cumbersome. And that was the majority of the reasons. And then you see in the lower part of that table that for related adverse events, treatment adverse events, you have exactly the same number for active and placebo. And serious related treatment adverse events were only 2, and severe related were only 4, and we didn't see any ARIA. So overall, the safety of varoglutamstat at 300 mg and 600 mg was very good. And I can add that there were actually, and that's an analysis we just got very recently, that there were no differences between 300 and 600 when you divide the dose.
There is no increase in adverse events when you move from 300-600 milligrams. Then on the left side, we summarize also what was most frequently observed, and that was COVID-19, actually. We had probably a quarter of the patients at least had COVID-19 infections. We saw some diarrhea, dementia, headache, and arthralgia, but only arthralgia showed the slight trend in favor of the drug. All the others were very equally distributed between the treatment arms. For your information, because COVID-19 can, of course, impair the cognitive performance at a certain level, we also looked at a non-pre-specified, so post-hoc analysis, whether COVID-19 patients with infection had a different outcome than those which had not. There was no difference if you would exclude the COVID-19 patients from the analysis.
The results on the primary and secondary endpoints stayed what they were if we look at all patients or only patients which had not a COVID-19. This is now the summary on the next chart, the summary of our key learnings in Alzheimer's disease. What we saw is no treatment signal at 600 milligrams twice daily. We lost the treatment signal, the efficacy signal we saw in SAPHIR in this study. The PK and QPCT inhibition in plasma and CSF showed that varoglutamstat can inhibit the QPCT enzyme and is a potent inhibitor and is also exactly represented on the target occupancy where it should be. The drug at 600 milligrams was very well tolerated.
And the key learning is probably that the slow uptitration led to a clear improvement in the tolerability if you compare it to SAPHIR while maintaining the overall favorable safety profile. So what are we planning now in early Alzheimer's disease? We announced today that we have decided to discontinue the VIVA-MIND study in the second half of 2024. And the reason is that we have, of course, the results of VIVIAD already, and they show at 600 milligrams no effect, and the patient population is very similar in VIVA-MIND compared to VIVIAD. And we will, of course, see whether VIVA-MIND gives similar data or different data. And we will then integrate all the Phase II data from SAPHIR, VIVIAD, and VIVA-MIND together to understand the dose response and then understand whether it makes sense to investigate and go to higher doses with varoglutamstat in early AD or not.
Then, of course, we also want to investigate a little bit the science behind QPCT pathways, looking at biomarkers and understanding what we actually trigger at these doses. That is the summary of varoglutamstat in early AD. Then I now switch to the kidney organs. Next slide. Probably I want to start with saying that kidney function was prospectively integrated via the protocol amendment before we unblinded the data. Based on preclinical findings we had generated and also published before on one of two compounds and internal assessments, and we thought that the kidney is a very good organ to look into that study because patients with Alzheimer's disease have comorbidities which reduce the kidney function and also age is a risk factor for impaired kidney function.
So our assumption was this patient has already some kind of impaired kidney function in that study, and we can study the effect of varoglutamstat on that impaired kidney function. But turning now to the scientific rationale, why could that be that a QC inhibitor can improve kidney function? And that is based on a lot of scientific publications where it is shown that many diseases are driven by inflammatory and fibrotic processes induced by a variety of stimuli, including metabolic, muscular, and autoimmune dysfunctions. In other words, all these disorders upstream and frequently had an inflammatory and fibrotic effect on the kidney, which then impairs the kidney function at the end, can lead to end-stage kidney disease dialysis or transplantation.
Many of those inflammatory and fibrotic pathways in the kidney require the formation of a pyroGlu version of a peptide to be fully inflammatory and to be fully pyroglutamated. Those examples are, for example, CCL2 or fractalkine, which has been shown to contribute to the progression of the kidney disorders. There has been published, I think, in 2021, a rat model in CKD where we can show that a tool compound, a QC inhibitor, in an animal model can improve kidney function and reduce inflammation in a glomerulonephritis model, including the urinary albumin-creatinine ratio. Therefore, when you see on the right side, you can see that if the peptides, the inflammatory and profibrotic peptides are pyroglutamated, they have a strong activity, and they're resistant against degradation. So they drive the inflammatory and the fibrotic process, and the disease progresses.
If you prevent the pyroglutamation, you still have the inflammatory peptides, but they are weaker, they are faster degraded, they are less potent, and you can stabilize disease and recover the disease, at least partially. We put that rationale in the protocol, and we defined the estimated glomerular filtration rate as a key parameter for measuring kidney function. On the next chart, let's go to the next chart. Just to make you understand what we did here, we followed the FDA guidance of measuring kidney function based on the estimated glomerular filtration rate, sorry, by creatinine. We measured it through slope analysis across 96 weeks. That is the recommended methodology on which the FDA usually bases the approval of drugs for kidney function. Also the FDA usually requires for kidney disorders a two-year duration.
Luckily, in VIVIAD, we have exposed patients up to two years. So these data are probably a very good proxy of what the drug can do in kidney disorders. Now I lead you to some results. First of all, we looked at the total population. This is 258. One patient didn't have a post-baseline creatinine value, so we couldn't measure that. So total was 259 patients, but 258 went in that analysis. And what you see is in the placebo group, the patients lost about 1.55 milliliter per minute per year. And in the active arm, they gained 1.92 milliliter per year. That means it's a change between the two arms of 3.5 milliliter per minute per year, per square meter, by the way. And that p-value is 0.001, or it's smaller than 0.001, based on only 250 patients.
Then on the right side, we carried out a dose response. And of course, in the dose response, you still have the same placebo value, but you see the differences between 300 and 600 milligrams. 300 milligrams basically shows a stabilization of the disease, whereas 600 milligrams shows a bigger improvement than 300 milligrams. And the difference between 600 milligrams and placebo was 4.16 milliliter per minute per square meter per year, with a p-value again below 0.001. And the representation here is patients as randomized into the study. Going to the next chart. We see here that we tried to identify patients with risk factors for chronic kidney disease, so those who have more inflammatory and fibrotic processes ongoing.
The way we defined it, we took all the patients who had type 2 diabetes at baseline or hypertension at baseline, which are known risk factors for kidney disease and which drive usually chronic kidney disease until end-stage kidney disease in many patients. We looked here at patients with risk factors on the left side and with no risk factors on the right chart. I want to start with the placebo group in patients with risk factors. You see that patients in the placebo arm declined by 2.7 milliliters per minute per year, whereas with no risk factors, they have on the right chart only 0.4 milliliters per year. This is a very credible value because patients who have risk factors, of course, decline much more than patients who have no risk factor.
Elderly patients who have no risk factor usually have a relatively stable kidney function and are at no risk of deterioration. But those which have risk factors have, of course, a risk of deterioration. That is well known. And when you look at the left chart, what the dose response is in patients with risk factors, you see a significant difference between 600 milligrams and placebo, again of value of 0.001. And you see that the difference is increased to 6.6 milliliters per minute per square meter per year. On the right side, you see that there is a very similar picture, but the effect size when there is no risk factor is, of course, much smaller and the improvement much less with 600 milligrams.
That is also very reassuring because it tells us if the pathological pathways of inflammation and fibrosis are not activated in patients with no risk factors, they have also a smaller effect size because the drug, of course, has very little effect if there's no inflammation and fibrosis. The drug has a much better effect in improving kidney function if there is inflammatory and fibrosis. So we believe these data are very credible and reliable, and we are very positively encouraged by these data. Going to the next chart. We summarize here the key finding and look ahead what we do. We believe that these data actually are transformational for our organization because we have the first time shown in a robust endpoint, which is accepted as a key primary endpoint for pivotal studies also by the FDA, that QC inhibition has a beneficial effect on health outcomes.
We would have wished, of course, that would have been observed in Alzheimer's disease. But in VIVIAD, it didn't happen. One explanation is that the dose was maybe too low for the brain. But we saw it very robustly in the kidney function. Therefore, we think we have a very good platform to develop our molecules further in kidney and other inflammatory and fibrotic disorders. That significant improvement is specifically noteworthy in patients with type 2 diabetes and hypertension as they are patients with improved risk or increased risk of end-stage kidney disorders. What will we do looking into the future? We, of course, will further analyze the data. We are only seven weeks after the key outcome data. So I think we are well advanced for seven weeks.
Of course, there are still some things to do and some way to analyze the data and look at subgroups and do some analysis which further increase our learning and our opportunities. We also will understand, try to understand whether we should do one or the other non-clinical study to improve our understanding of the pharmacology of the drug in kidney disorders and other inflammatory disorders, and understand the pathways behind the QC inhibition. Then we will create a clinical development pathway for varoglutamstat in kidney disorders. Of course, if we would do further clinical study, we would require funding or collaborations for this. That is then our business target in further moving forward kidney disorders and analyzing the potential for early Alzheimer's at higher doses. I want to switch to Anne to conclude this meeting. Please, Anne. Thank you, Frank.
I will now walk you through a few financial highlights for the year, and importantly, our cash runway. Reflected in our 2023 financials is careful and selected spending through the year as we worked towards the VIVIAD readout in the first quarter of 2024. What you see in the revenue line is a EUR 3.6 million reversal in license revenue. The reversal is related to license revenues recognized in 2021 from our partnership with Simcere, which had included a variable milestone payment of EUR 3.6 million based on the initiation of the first human clinical trial of varoglutamstat in mainland China. After reassessment of the anticipated first milestone payment, it is expected that this trial will not start before further clarity from an in-depth analysis of the VIVIAD results, as well as from additional analysis of the full data and its implications.
As such, we have impaired the milestone with the respective revenues being reversed. This reversal is non-cash, as was the milestone in 2021 at that time. R&D expenses amounted to EUR 17.6 million this year versus EUR 20.2 million in 2022. This decrease is primarily attributable to lower manufacturing costs of EUR 3.6 million, which is partially offset by higher clinical costs of EUR 1.7 million, mainly due to the progress of the Phase 2b VIVIAD clinical study. We have also seen a decrease in G&A expenses with costs of EUR 8.6 million in 2023 compared to EUR 8.9 million in 2022. This decrease is largely due to the release of EUR 2.6 million of previously capitalized capital raising costs in 2022, partially offset by EUR 2.2 million higher expenses for personnel, legal, and consulting, as well as costs for non-executive directors.
All of this resulted in a net loss for 2023 of EUR 28.3 million compared to EUR 28.2 million in 2022. On this next slide, I would like to highlight selected KPIs. Most importantly, the company held EUR 18.6 million in cash and cash equivalents as of December 31st, 2023. This cash should be combined with our term deposits of EUR 10 million when considering our total liquid assets of EUR 28.6 million. This is compared to cash and cash equivalents of EUR 26.6 million as of December 31st, 2022. Our cash runway now extends into the second quarter of 2025, reflecting an overall reduction in cash utilization. But how do we actually get there? As you can imagine, the majority of our spending has been associated with varoglutamstat in early AD. VIVIAD spending is ramping down in the near term as the study comes to a conclusion.
Furthermore, we have decided to discontinue VIVA-MIND in the second half of 2024, as well as stop VIVALONG preparation activities and API manufacturing campaigns. As Frank has been outlining today, we believe we have exciting data with varoglutamstat and kidney disease. This cash runway should allow us to put the pathway together to explore this initiative and additional opportunities. However, clinical studies will require further funding or partnerships. In addition, this would also be needed to extend our cash runway beyond the second quarter of next year. I'd like to conclude by reiterating our continued dedication towards unlocking the potential of our lead asset, varoglutamstat. Based on the very encouraging kidney data from VIVIAD, we are shifting our research and development focus towards inflammatory and fibrotic disorders.
We're particularly excited about the opportunity in kidney disease with a strong proof of concept in improving kidney function observed in VIVIAD biomarker analysis. We are moving forward at a quick pace to create a development pathway in kidney disease. In early AD, we will continue to analyze incoming data, as well as looking at the totality of the Phase II data in early AD, and are assessing a development path forward for varoglutamstat at a dose higher than 600 milligrams BID. At the same time, we continue to explore select early-stage pipeline programs. Moving forward, prudent financial management remains a priority for Vivoryon. And we were able to extend our cash runway into the second quarter of 2025, as I've just detailed. We are also actively pursuing funding and business development opportunities to support varoglutamstat and our realigned company strategy.
We look forward to keeping you informed on our progress. With that, we'll now open the call to take questions. Thank you.
Thank you. Dear participants, as a reminder to ask a question, you will need to slowly press star 11 on your telephone keypad and wait for a name to be announced. To read your question, please press star 11 again. Please stand by. We will compile the Q&A rows. This will take a few moments. Now we're going to take our first question. It comes from Luisa Morgado from Van Lanschot Kempen. Your line is open. Please ask your question.
Hi, team. Thank you for taking my questions. I have two questions. First one, on the next steps for assessing varoglutamstat in kidney disease, do you have any timelines on this?
So when are we going to hear a bit more about it? And my second question would be, in terms of assessing varoglutamstat in higher doses, higher than 600 mg, what would be your approach here? Since we've already seen some tolerability issues, would you tackle that only by adjusting titration or anything else? Thank you.
Okay. Let's start with the second question first. We have now, of course, much more safety data. And what we can say is that with the titration protocol we have implemented in VIVIAD, we have probably eliminated most of the safety issues. So by slowly titrating the drug up, most of the safety issues disappeared. And we looked, of course, at the safety in the titration period versus safety at the full dose period.
We didn't see any meaningful difference in the titration period between the drug and placebo, which means titration is totally safe. There we didn't see safety differences between 300 and 600. Actually, 300 was a little bit worse than 600, which is a little bit counterintuitive, but it's not meaningful differences. I think we can say the titration contributes a lot to the safety. We saw that also in the VIVA-MIND study. We have a little bit of different titration regime, but we also saw good safety. Our conclusion is that the titration is necessary for that mechanism of action. The speed can vary a little bit. We can still play a little bit with the speed of titration. That is probably taking out a lot of problems we saw in SAPHIR. We basically more or less immediately went into the full dose.
Therefore, we believe, based on this larger safety database, there is likely room for going higher. I don't think there's any prohibitive finding. I think we will have a better titration, a better tolerance. But of course, that has to be studied and confirmed. The second question, kidney. Of course, we are super excited about the kidney. We do a lot of additional analysis. We have a lot of biomarkers still ongoing. I think a good next point will be when we have first quarter earnings. I think that is a milestone we set ourselves to. We haven't announced when it is. But at the first quarter earnings, we have probably some more data. We will not have all the data, probably. But we can enrich our finding at that point in time. And yeah, and show the robustness of our findings.
Did I answer your question?
Yes. Yeah, that was very helpful. Thank you.
Thank you. Now we're going to take our next question. Just give us a moment. The next question comes from Samir Devani of Rx Securities. Your line is open. Please ask your question.
Hi, Frank. Hi, Anne. Thanks for taking my questions. Thanks for the detailed presentation. I guess I wanted to just dig in a little bit deeper on the kidney disorder opportunity. Some of the data you've presented look quite interesting. I guess the 6.61 milliliter improvement that you're seeing after two years, I just wondered if you could maybe qualitatively just tell us, has that plateaued earlier, or is it still improving at two years? Maybe you can give us some perspective on the clinical relevance of that improvement.
Okay. So first of all, the way you analyze the data for a regulatory scientific purpose is to make a slope analysis. And these are annual improvements. So it's per year. So you run it two years, probably more. But these are trajectories based on all the data points you have. And of course, there's variability between patients and so on. And the way the curves go is that varoglutamstat mean values always stayed above the baseline. So you have always a better result at any observation time point than at baseline across the two years. And the placebo curve, of course, declines. And it declines at a speed of 2, 3, 4 milliliter per year. And so what you see is that there is across two years, and longer we cannot say because longer we haven't studied, there is a consistent mean improvement above baseline.
There is a meaningful and even statistically significant decline in the placebo group in patients at risk with kidney disease or with hypertension, diabetes, which is expected, by the way. It's not a new finding that's actually expected. The difference, of course, is a widening difference if you look at the slope analysis. If you look at the observed case analysis, it is widening and constant, I would say.
Can you tell us what the baseline eGFR for the overall population and then just the subgroup was?
Yeah, sure. We have not now I mean, we have not fully analyzed the subgroup baseline eGFR severity. That is something which we will announce later. But I can tell you we have patients the majority of patients were in the 60-90 mL eGFR group. But we had patients below 60 mL also.
And we have some patients above 90 milliliters. Above 90 liters is fully normal. Between 60-90 is a minor impairment. And below 60 is already starting a major impairment of the kidney function. And this is what we saw. And about the mean value is about 80 between 78-80. And it's, of course, a little bit lower with patients with diabetes and hypertension than it is in the patients without this risk factor. So there's a difference about 5 milliliters.
Okay. That's great. And then I guess moving on to you mentioned the paper that was published. And I believe there were some Astellas researchers exploring PQ529 some time ago in glomerulonephritis. So I guess I'm trying to understand what happened. There was obviously some collaboration with Astellas at that point. Perhaps you could just tell us what happened. What's the differences between PQ529 and varoglutamstat?
Is there any, I guess, prospect for any other compound in Vivoryon's portfolio that might be more suitable than varoglutamstat to explore further?
Maybe answer the second part and give Michael this for the first part. The second part is 529 is very similar to 912. To varoglutamstat, it is basically a tool compound we use specifically when we go to very exploratory new situations in order to keep also the records clean for our regulatory compounds. But from a pharmacological activity, it is basically a selective important inhibitor of QC and iso QC. And it's very comparable between the group compounds. So Michael, if you want to.
Yeah. Hi, Daniel. This is Michael. Nice to talk to you again.
Hi, Michael.
Hi, Michael.
Yeah. I mean, the difference is basically or let's say PQ529 was drawn out of the, let's say, development candidate process also because it was not really possible to come up with an enantioselective synthesis for this molecule. So it's basically really just a tool compound. And PQ912 is much more suitable for production also on larger scales. And to be clear, there's no other company with any rights to the kidney applications of the QC inhibitor portfolio that you have? Pardon? I didn't get the question.
Just clarifying that Astellas doesn't have any rights or No, not at all. I mean, it's No, not at all.
So I might want to add on I might want to actually add on that point even. I think we don't have to disclose that.
But we also filed, of course, appropriate medical use claim patents for the application in kidney diseases for our compounds. So that's also an important point, I think, important step, which solidifies our position here.
Okay. That's great. And then just my final question is really just you mentioned that you wanted to do some additional biomarker analysis in the kidney disorder opportunity. What do you mean by that? What additional analysis are you looking to do?
We would probably call for kind of so if I answer the question, I would say also for IP reasons, I would probably not want to go too much into detail with that. But of course, we will look into kind of the obvious biomarkers in that field. But maybe Frank want to add on that. I think we want to keep that still secret.
I mean, we have selected, of course, a couple of biomarkers which are on the pathway of the glutaminyl cyclase in that area. But I think it's too early to disclose it. We also have not the results in-house. So we will do this diligently like we did today with the data. We don't hide data. But what we don't have really and what we probably need to use for substantiate our intellectual property, we don't want to disclose now if you can understand, please.
That's understood. Thanks very much.
Thank you. Dear participants, as a reminder, if you wish to ask a question, please press star 11 on your telephone keypad and wait for a name to be announced. And now we're going to take our next question. And the question comes to line of Marcus Scherhag from Hauck. Your line is open. Please ask your question.
Yes. Good afternoon. Thank you for taking my question.
Can you hear me?
Yes. Frank? Yeah, sure.
Yeah. Okay. So my question would be on these surprising kidney results that you presented to us, what do you think is the pathway forward? Because my question would be, do you think that this data plus the data that you will further collect in the next weeks, will this be sufficient to find a partner? Because it's probably quite difficult to imagine doing kind of capital raise at this current share price. So do you think that this data is strong enough to find a partner for this?
Well, how can I know what other ones? This is a question I cannot really answer.
But what I can give you is, I mean, everybody can look at market capitalization of companies who are in the kidney field, either in Phase Ib or IIa or in the later stage, what the M&A activities were in the past. I think kidney disorders in general are commercially even more attractive than Alzheimer's. There are many more people with kidney problems than there are with Alzheimer's problems in the world. The disease is extremely expensive when you go into dialysis. And in kidney transplantation, it is extremely bothersome also. So I don't think it is a step backward when we go from if we would go away from Alzheimer's, what we haven't announced because we still need to analyze data. We have still a study coming. But if we would shift fully to kidney, that's not a step backward from a commercial perspective.
What other companies are interested in playing with us? I cannot comment on this because it's, first of all, much too early. Second of all, I'm not other companies. I think we need to build from our own strengths, from our own science and our own data. And then we can see what is the development pathway. We also didn't announce today where we would go in kidney disease and how we would do it. That is dependent on further analysis and another public statement later this year. But of course, we are working on this, what is in our mind. And then there is still a little bit of time. It's just seven weeks after we saw the top-line data. It's probably four weeks after we or three weeks after we saw the first kidney data, not even those which are presented to you.
So this is incoming news every day. And I don't want to jump the gun now to say, "we go there and there and there." Let us a little bit of time to consolidate the data, to make an attractive package, to understand where we best go and where the drug fits best to the patient needs. And then we're going to see what happens.
Okay. Well understood. Then just maybe as an add-on to give us a little bit more flavor because many people are not that experts who are invested in the stock. Can you give us a little bit more flavor of how significant and how strong this data is?
Well, what can I say?
If you look at the current standard of care in kidney disease and look at the current molecules which are used, including SGLT2 inhibitors or the GLP-1 of Novo Nordisk, who had a kidney study which will be announced now in Stockholm at the European Kidney Congress, they all only show a reduction in progression. There is no approved drug and no drug probably in major development which shows an improvement of eGFR in a placebo-controlled study across with probably the exception of 2, at least to my memory. There can be more. Don't kill me. But one is a cell therapy, which is an autologous transplantation from the kidney. They had some Phase IIa data. Then they showed some improvement in eGFR. But it is a population of probably 50 patients. And it goes over 1 year. And the second year was not placebo-controlled.
The second study was a drug from Reata, which actually is called bardoxolone, showed a continuous improvement of eGFR over nearly two years. But the drug had some safety issues. Additionally, it didn't improve the urinary albumin-creatinine ratio. So it actually didn't improve on the protein loss for the kidney and didn't change the number of end-stage kidney disease. We have, at least in the preclinical setting, shown in the publication that also show an improvement of the urinary albumin-creatinine ratio. So that is quite a good finding. And we are reassured that we can differentiate from these other two compounds which have shown some improvement. So I think we are quite unique in the current situation in the kidney field, with showing an improvement above baseline over two years. And I think that gives us a reasonable, strong position to move forward.
That's probably what I can say at that point.
Okay. And then, sorry, last question from my side. Just to understand correctly, would you want this side to go into a clinical phase given the fact that you have already done the Phase I and IIa and VIVA-MIND studies? At which point could you enter starting a study for the kidney?
We consider us a clinical stage, mid-stage, Phase II company with now having a proof of concept in an endpoint which is accepted by the FDA in kidney disorders. What is the next study is depending on the development pathway. And just to give you a little bit more flavor to this because you want that on concrete. So if you would go in chronic kidney disease stage 3B and 4, of course, these are huge studies with probably a couple of hundred patients, maybe even thousands.
If you go to more of an orphan drug setting, of course, you would start differently with lower patient numbers and probably start a little bit more advanced. But these decisions depend, of course, on further analysis of data, consultation of experts, and understanding of the financial needs, and so on. So this is analysis which we still have to do. And this is why I said we are looking for a development pathway. But in kidney disorders, there is a lot of options. This is not only the big indications of CKD 3b or 4 or even 5 you could go, but then you probably need a few less patients. Or you go in an orphan. And there is also other fibrotic aspects we can touch in kidney disease and others. So there are decisions which are still ahead of us.
And that requires a very diligent review for which we had actually not the time until the results came in until today to be really specific on this. And I'm sorry, apologies to be a little bit evasive on this, but it's just a fact.
Okay. Thanks.
Thank you. Dear speakers, there are no further questions for today. I would now like to hand the conference over to Frank Weber for any closing remarks.
Oh, yeah. I see that there are a lot of other people who want to ask questions, but the time is over the hour. I'm sorry that we couldn't take all the questions today. I understand the transformation of the company raises a lot of, yeah, curiosity. And we are very happy about your interest. Those who couldn't ask a question, I would please to send it in writing per email to our investor relations team.
We will immediately come back to you either in writing or scheduling a telephone conference with you because, of course, you may have very specific questions, remarks or recommendations for us. We are very happy to hear all of that. With that, I want to wish you a very happy day. Thank you for your interest in the company. Goodbye.
This concludes today's conference call. Thank you for participating. You may now all disconnect. Speakers.