Good afternoon. Our last presentation before we all break for lunch, and we're very happy to have with us Vivoryon Therapeutics, which will be represented by the CEO, Mr. Frank Weber. For those of you who don't know the company, Vivoryon is a clinical stage biotech company focusing on developing innovative small molecule-based medicines, especially for the treatment of inflammatory and fibrotic disorders of the kidney, as you can see on the presentation picture already. Like always, we will have a 30-minute time slot allocated for this 20 minutes presentations, 10 minutes Q&A. If you have any questions, feel free to use our chat box on the lower right-hand corner, and we will record this event, and you will be able to review it on our research hub later this afternoon. With this in mind, I hand it over to Frank. The floor is yours.
Thank you, Mr. Nass. Dear ladies and gentlemen, thank you for your interest in the presentation. This presentation is about improving the kidney health outcomes by innovative new pharmaceutical treatments developed by Vivoryon Therapeutics. I need to do this myself. The disclaimers: we are a publicly listed company and have the typical disclaimers. Now, why the kidney? The kidney is the most frequently replaced organ worldwide during human lifetime, meaning that nearly 4 million people are on dialysis worldwide, meaning their kidney function has already expired, and they need an artificial kidney to maintain their function and to keep them alive. As an alternative for kidney dialysis, we have kidney transplantations, and more than 110,000 kidneys are transplanted annually, with the numbers of 2023 estimated to increase, but there is an equal number of patients or higher waiting for transplants, so that number actually should be higher.
Also, we need to consider that while these numbers are already extremely high, they should actually be much higher because in many developing countries, patients do not have access to dialysis. They have no access to therapy and therefore actually have to die due to kidney failure. Just to give you a context, the other organ which, in the modern world, in the Western world at least, gets replaced quite frequently is about the hip, and we have about 1 million hip replacements every year, and all other organs function much better, like the liver and pancreas, and there are much less organ replacement needed for that. Also, to keep in mind that when you get a kidney transplant, the average age is 53 years, so the kidney failure comes in quite early in the transplant patients.
The dialysis patient usually is a decade later, so transplant patients, dialysis patients start the dialysis usually at the average age of about 64 years. Kidney fail frequently, and therefore chronic kidney disease, that is the stages before the kidney fails and needs to be replaced, is a very frequent disorder. About 1 in 10 adults in Europe are affected by chronic kidney disease. That are the stages before you get a kidney replacement. Once the kidney replacement is done, it costs about EUR 80,000 per year if you're on dialysis. Hemodialysis can be a little bit cheaper, can be a little bit more expensive depending on what type of dialysis you get. In Europe, about EUR 140 billion are spent annually on treating CKD and kidney failure, so it's a huge amount of healthcare costs which are dedicated to treat kidney health.
End-stage kidney disease, despite this high number but proportionally relatively low number, takes about 2-3% of the healthcare budgets overall. Finally, there is an environmental problem because dialysis generates a lot of carbon emissions in Germany, around 1.24 billion kilograms, so in tons, of course, less. It is only a million, but that is about the carbon footprint of 700,000 cars. Dialysis is quite an energy-exhausted procedure and should, of course, be avoided if possible. Why is chronic kidney disease and kidney failure so prevalent, and how will it develop in the future? The number of patients with chronic kidney disease and the burden of disease is expected to increase globally in the next decade from about 0.75 billion to 1.2 billion when they are in terms of aging. In terms of hypertension, the number of patients increases. In terms of diabetes, these patients increase.
The main risk factors for chronic kidney disease are diabetes, high blood pressure, age, because the older you get, the more likely the kidney surrenders to the toxins of diabetes and hypertension. There are also rare disorders, inflammatory rare disorders, which create chronic kidney disease and kidney failure like glomerulonephritis or cystic diseases. There is also a part which is still unknown and has not been discovered. As the number of patients with diabetes and hypertension increases and the population ages, the number is expected to increase in patients with CKD. That leads, of course, not only to more patients, it leads also to more cost.
These costs will be largely derived by an increase in dialysis cost, an increase in transplantation cost, an increase in more patients being treated and diagnosed earlier, and of course, new therapeutics entering the market and trying to prevent the dialysis and the transplants. The market is clearly increasing about fourfold in the next 10 years with the increasing epidemic of the disorder. On that background, we can look now at what types of therapies are available today. What can patients get treated today to address this global health challenge and financial challenge for the system? There are currently a couple of therapies available. One is the angiotensin receptor blockers or converting enzyme inhibitors, which are usually used to treat blood pressure, but they're also effective in a certain way in chronic kidney disease.
There are the gliflozins, or called SGLT2 inhibitors, which are approved for treating chronic kidney disease. There are products like GLP-1s, like semaglutide, which improve kidney function. What does it mean, improve kidney function? As you see from the graphs, you see the untreated patients in placebo, and you see the treated patients with the active treatments, and you see everybody still declines. All the treatments today just reduce the speed of progression of about 30-40%, but do not stabilize the kidney function and do not improve the kidney function slightly. Patients at the end still end in chronic kidney disease, in end-stage kidney disease, need dialysis, and they need kidney replacement and kidney transplant maybe two, three years later, maybe four years later, maybe one year later, depending on how good the medication works in the individual patient.
They still get there, and that does not change the overall epidemiology and forecast of how this disease will develop and affect us all. Now, what can Vivoryon do in this setting? Vivoryon is a mid-stage biotech company, actually phase II clinical test stage, and we are aiming to transform the treatment of kidney disease with a novel drug candidate, varoglutamstat. We have clearly shown the medical need, which is actually to stabilize the kidney function at the stage where the patient is diagnosed, maybe slightly improve it, and keep it stable for many, many years so that the patient does not further decline in the kidney function and the patient does not need kidney replacement therapy in end-stage kidney disease. Now, what is the solution?
We have a medicine candidate which is called varoglutamstat, and it's a first-in-class QPCTL inhibitor, and I will be more detailed on the next slides what is it about. Varoglutamstat has shown a unique potential to stabilize and partially recover kidney function, shown the first time, I think, in the development of new medicines, based on two international clinical studies which were conducted independently, and I'll show you some of the data we have generated so far. The opportunity is that we have developed a clear path to the market in a large and growing global population with an initial target to treat patients with diabetic kidney disease. What is the technology we have developed? How is varoglutamstat working, and what is the evidence that the drug really stabilizes kidney function and improves kidney function?
The discovery is that we have a lot of peptides in the body which drive inflammation and fibrosis, which leads to kidney failure. Kidney failure, if you have diabetes or hypertension, usually develops based on inflammatory and fibrotic processes which at the end lead to organ failure. These peptides need to be pyroglutamized at the N-terminal end to be fully functional. In order to be really inflammatory and fibrotic, they need at one end of the protein ring a pyroglutamate version, which is depicted on the left part of the slide. Peptides without that pyroglu version are much less inflammatory and fibrotic and cannot drive the kidney failure and fibrosis as well as the pyroglutamized versions. We have developed a glutaminyl cyclase inhibitor which prevents this pyroglutamization, the activation of these inflammatory peptides to drive kidney failure and fibrosis forward.
In other words, our little molecule varoglutamstat blocks the enzyme which converts peptides to the pyroglutamate version and therefore stops the inflammatory and fibrotic process and can improve partially the kidney function, eGFR, even above the initial stage. How do we come to that evidence? The company conducted two clinical studies, one in Western Europe called VIVIAD and one in the U.S., which was sponsored by the NIH in the U.S., called VIVA-MIND. The primary objective of the study was looking at Alzheimer's disease, but the drug did not work in Alzheimer's disease, and the secondary objective was looking at kidney function. We developed a strong proof of principle in over 360 patients treated up for two years in these studies, which provide an excellent base for the development in diabetic kidney disease. How did we get the data?
The kidney function was measured prospectively using the glomerular filtration rate, the eGFR, which is a key regulatory endpoint, which is the primary endpoint you need to show in study, and that was measured prospectively in the study and included as a pre-specified endpoint. The results were statistically significant and clinically meaningful, and I'll show you that on the next graph. The effect kicked in after six months, so 24 weeks, and was sustained over two years until the end of the study. The improvement was confirmed in meta-analysis, pooled analysis, re-analysis. We measured the eGFR in three different ways, and it was always confirmed. Finally, the drug was very well tolerated in more than 400 study participants exposed so far. Here are the results of eGFR in the two studies.
You see that the active arm, which is here in pink, goes up, and up is good, so it improves the kidney function, improves the filtration rate. It goes up and stays up through the whole period of two years, whereas the yellow curve, which are the untreated patients, go down and they are expected to go down and further and further decline. The difference between the yellow and the pink becomes statistically significant at week 24, and the p-values are maintained until the end of the trial. As the study was double-blind placebo-controlled, nobody knew who was active and who was on placebo. These are the safety data of our studies, and as you can see, the same color code. Pink is the active group, and yellow is the placebo group. TEAE is Treatment Emergent Adverse Events.
Many patients had them, but there was virtually no difference between the two. Investigators or doctors could decide whether they thought they are related to the treatment or not, and also here you see no big difference. Also at the serious adverse event and the related one, you even cannot see the serious adverse event related because they were virtually not existing. The study drug discontinuation was very low, with less than 7% of patients stopping the treatment within the two-year timeframe. Overall, the tolerance of that drug is very good, and we have, of course, completed also prior studies, meaning a phase I study before and a human ADME study that looks at the metabolism of the drug is also completed. Of course, we have the preclinical data package in toxicology and safety to treat patients long-term.
Overall, the safety database is well established. Now we compare the effect size of varoglutamstat with the current available treatments for kidney disease. You see two bars. One is the pink bar, which shows you the eGFR, and the yellow bar is the proteinuria, which is a secondary endpoint usually in the study. The primary endpoint is clearly the pink bar. That is the regulatory relevant endpoint. You see the SGLT2s, which are currently standard of care, give you about 1 mL. The GLP-1s give you about 1.5 mL. The mineralocorticoid antagonists give you about 1 mL or 1.5 mL. We show a difference of more than 5 mL between placebo and active. We have not yet measured the proteinuria. These data were not prospectively collected in the study, but we are hopeful that this goes in the same direction.
For the primary endpoint, we can clearly show that varoglutamstat has about a four to five-fold bigger effect than any other of the approved treatments today. Because kidney is a very interesting area, also from a commercial standpoint, there is a lot of merger and acquisition dynamic in the area. There are not so many pipeline projects, but once there is clinical proof of concept and strong data in phase II, M&A is often happening. As you can see, in the last years, new therapy popped up, and these companies, many of those, were then acquired by larger pharma companies who are interested to develop drugs in this area. Looking at the market exclusivity and the value of the asset, we have a new composition of metagranzit, which runs until 2044, with a potential patent extension probably until 2049.
We have also medical use patents, dosing regime patents, and combination patents with SGLT2 inhibitors, which all run until about 2050. We have more than 20 years' market exclusivity ahead of us, and that allows a long commercialization period and exclusivity period without generic competition coming up early. Sorry, I can't move the slides anymore. Yeah, no. What we do now is we do one more clinical study to look at more advanced patients with diabetic kidney disease than we have treated in the previous two studies I showed you. We are specifically designing now a study to look at stages III and IV of diabetic kidney disease on top of a combination of SGLT2 inhibitors or standard of care in order to confirm the efficacy of varoglutamstat also in later stages of chronic kidney disease and diabetic kidney disease.
That study is adequately powered with about 100 to 150 patients. Patients are going to be treated about 12 months. The top-line data will be available about two years after the start of the study, and the design could include an interim analysis at 15 months to give an earlier proof of concept. Typically, such a study would cost about EUR 12 million-EUR 18 million, depending on the final patient numbers. Why invest in Vivoryon at that stage? We have shown there is a high medical need with no therapies available for kidney disease and diabetic kidney disease, which can stabilize kidney function long-term, but varoglutamstat has shown that. There is a sizable population in major markets in the U.S., Europe, and globally. Many patients wait for such a treatment.
There's an attractive opportunity in kidney space with excellent collaboration opportunity with big pharma once the next study results are available. We have, from a company point of view, a robust clinical evidence and two independent studies with a large and unprecedented effect size. We have a new mechanism of action with excellent clinical pharmacology results in animals supporting the results we have seen in humans. The next study has a low-risk design and has an attractive short readout period within two years, and there is an experienced management team with a proven track record in developing new drugs. With this, I have ended the presentation. I thank you for the attendance. I hand over to Mr. Nass.
Thank you so much also for the insights into your developments and congratulations on what you've accomplished so far. A quick couple of questions for the financial community.
You said the trial that you're now embarking on usually costs between EUR 12 million-EUR 18 million. Can you say a few words on your current financing situation?
Yeah, the company has cash until January 2026, and we will need to find money for that study, and we need to look for collaborations and investors to finance the next study. We are debt-free. We are listed, and we wait for investments.
Thank you. When do you expect market entry of the drug in the market?
The regulatory pathway for such a disease is very well established. After the next study, there needs one more phase, which is called phase III. These phase III studies take about three years to complete. They have a treatment duration of two years with eGFR as a primary endpoint, so it's about a three-year study to be completed.
We think that in the early 2030, the drug can reach the market.
All right. Thank you. You would probably partner with a manufacturer-distribution pharma company to bring it to market.
Yeah, Vivoryon currently is a small biotech company and is not capable to commercialize in such a big indication worldwide. We would look specifically after completing the next study at a commercialization and development partner to lead the program forward.
Great. Thank you. I have a question from the audience, and I'm going to read it because it was written very nicely. Hello, and thank you for the opportunity to participate in your Q1 report. You mentioned being in substantial discussions. Could you please clarify what this means in concrete terms? Is there a timeline for when these discussions might be concluded or when we can expect further updates?
I think this is very nicely written. Your work continues to be truly impressive and exciting. Thank you for that.
Thank you. There is, of course, a discussion, should we enter a pharma collaboration now, or should we wait until the next study? This depends, of course, on the type of offers we get and the type of collaborations we can enter and the valuation we get today and we can get tomorrow. This is, of course, to be seen in the interest of the current shareholders and the future shareholders. That decision is, of course, not necessarily an easy one, but we are very diligent in keeping all options open.
We are discussing with pharmaceutical companies potential collaborations, but the question is whether at that stage it is the most attractive for the shareholder to go forward or whether we should not finance the next studies ourselves. We have done much bigger studies already. We are capable of doing that type of study within relatively short time with the CRO and then have a collaboration agreement thereafter.
Great. Given the, and of course, drugs usually have a very long development phase, as you alluded to earlier, are there any competitive products that are also in the pipeline that could hit the market around the same time or earlier, or are you the only one that is currently under development?
We are the only one with that mechanism of action.
There, of course, given the millions of patients available, there are other drugs under development, not necessarily ahead of us, but probably on the same or similar level. None has results as us, so from the effect size, we are leading the pack. There is probably expected one or two drugs with new mechanism of action, minor improvements, probably also hitting the market. It is, of course, not necessarily a crowded area, but it is an area where a lot of players try to go. Diabetic kidney disease, despite being the biggest of the chronic kidney diseases, the biggest in terms of numbers, is actually relatively empty in regarding pipeline, and there is not a huge amount of competition if you compare it to other areas.
Another question that was asked by the audience, which is basically going in the same direction but from a different angle.
It's not talking about competitors' products for kidneys, but it is asking, since the key reason for kidney failures are high blood pressure and diabetes, do you see that there are drugs on the market that could cure those two issues and thus make your product redundant?
Yeah, this is a very good question. It seems so with the GLP-1 agonist with Lilly and Novo selling billions and also the SGLT2s, insulin, and what have you, and a lot of high blood pressure drugs that kidney failure should go down, but it does not. Once you have the kidney in an inflammatory fibrotic state, it is self-propagating and partially resistant against major intervention, except for our mechanism, which has shown to stabilize the kidney. Usually, the kidney progression goes on despite that you get the diabetes and the blood pressure quite well under control.
To tell you that most of our patients in the study had normal blood pressure, and most of our patients in the studies we showed you had normal blood sugar levels, but still the kidney progresses once it is inflamed and fibrotic.
Great. Given the time, one more last quick question that is the drug that you're currently developing. If you partner this or should you maybe sell it at an earlier stage than before you enter the market, do you have other drugs in development, or do you see yourself basically dissolving as a company? Or what do you think could be the future of the company if you sell the product that you're currently developing?
Yeah, I was an executive committee of another company, which you call One Trick Pony, and I was interviewed, and we had basically only one or two assets.
The fate of that company was a sale to Roche a couple of years ago for EUR 8 billion-EUR 9 billion. At Vivoryon, the situation is not so dissimilar. We have more QPCTL inhibitors in the pipeline. We have a follow-up molecule, which slightly improves characteristics for varoglutamstat in the pipeline, which we can develop. I assume that somebody who enters a collaboration with us will also secure the rights of the follow-up compound and does not leave it for a competitor. I would think that a collaboration agreement after the next study is completed would encompass also what we have in the earlier pipeline and early research or early development included. That usually ends more in an M&A area, which was typically also shown in the kidney space. Most of those transactions were mergers and acquisitions.
There are also some licensed deals, but the biotechs I've shown you were all acquired by pharma, including the patents and the technology. More likely is probably an M&A than a licensed deal, but you never know, of course, until you have done it.
All right. Thanks so much. Unfortunately, we're out of time. I appreciate you sharing the investment story and giving us some insight into Vivoryon. I thank you, everybody, for attending this, for your great questions, and of course, wish you a very healthy lunch. We will come back in about an hour for our next presentation, which will be Viremet Medical. Until then, enjoy yourselves. Frank, thanks so much for everything. Staying on the line for a second, that would be great. Thank you.
Thanks for the audience, for the interest in the company. Thanks, Mr. Nass. Goodbye. Good.