Vivoryon Therapeutics NV

AEX:VVY

Earnings Call Transcript

[Operator]

Good day, and thank you for standing by. Welcome to the Vivoryon Therapeutics Third Quarter Results 2023 Earnings Call. [Operator Instructions]. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Anne Doering. Please go ahead.

[Anne Doering, executive]

Thank you, Nadia. Good afternoon, and thank you for joining us today for Vivoryon's conference call to discuss the company's third quarter 2023 results and operational progress. This morning,Vivoryon issued a press release reporting its third quarter of 2023 results, which is posted on the company's website at www.Vivoryon.com. On the call with me today are Vivoryon Chief Executive Officer of France Weber; and Florian Schmid, our Chief Financial Officer. Also, with us on today's call and available for questions is Michael Michael Schaeffer, our Chief Business Officer. We will begin today's call with opening remarks from Frank on Vivoryon clinical research and operational progress. Then Florian will review the financial results for the third quarter of 2023, and I will walk you through key catalysts and concluding remarks. Following the prepared remarks, we will host a Q&A session. Before we start, I would like to remind you that during this conference call, we will present and discuss certain forward-looking statements concerning the development of Vivoryon technologies, the progress of its current research and development programs and the initiation of additional programs. Should actual results differ from the company's assumptions and suing actions may be different 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. With that, I will now turn the call over to Frank.

[Frank Weber, executive]

Thank you, Ann. Thank you, Nadia. Good afternoon, good morning, everybody. Let's go into the activities of Vivoryon. Vivoryon is actually defined by 3 main assets. And that is our molecule and our approach. That is the development program. So how we develop that asset and that molecule and who we are, so the team, which actually does that activity. And we believe that we are very, very strong in all of these 3 main areas. So our approach is stopping the production of neurotoxic pyroGlu-Abeta to treat early Alzheimer's disease, and that mechanism, we consider validated targeting all key hallmarks of Alzheimer's disease, like the Amyloid, the tau and the neuroinflammation parts of it. We do not have with our small oral molecule the constraints of the monoclonal antibodies, meaning that we do not need infusions. We do not have product-related areas. We do not have imaging needs and that reduces cost and efficiency of the treatment. And finally, the market is very significant with a very high unmet medical need. There are millions of people waiting for efficient and well-terated therapies. Our approach is very robust. We have 2 Phase II sales ongoing. They're progressing very well. The European VIVIAD study has been fully recruited and we expect the final top line readout during the end of the first quarter of 2024, confirming what we have said before. And then we have the American [indiscernible] study, where a recent DSMB decision allows us to continue with the 600-milligram twice-daily dose, which is exactly the same dose as we use in VIVIAD just with a slightly faster titration regime. And finally, the team and the people working at Vivoryon, have a strong discovery development and management background, having broad multiple drugs already to the market. We have a healthy cash runway into the second half of 2024. And we have the ambition to become and be the leader of oral small molecule QPCT-Inhibitors. Going to the next chart and the news of the quarter more in detail. The highlights of the third quarter and the post period were in the order probably of relevance. The first is, of course, the VIVIAD study, we stay laser-focused on delivering the results at the end or during the end of the first quarter 2024. We can confirm that we have low discontinuation rates due to AE as well as overall discontinuation rates, and I will come to that on the next chart more in detail. We also can confirm that the statistical power of the study is above 80%, which confirms the design of the study. And we are already starting preparing an end of Phase II meeting with the FDA, which we plan to happen in the second half of 2024 presenting and leveraging the VIVIAD data. Next is the VIVA-MIND study, which is the Early AD study in the U.S. We are very, I would say, happy and relieved, I would also say that with the 600 milligrams twice daily is also well tolerated and acceptable in a faster titration regime, we use in the U.S. study compared to the European study that speaks to the tolerance and the safety of our vital start as we give it today. The adaptive design and positive DSMB decision supports a potential expansion to Phase III. I need to be a little bit specific on this. We -- in case VIVIAD study is positive, we have the intention to upgrade the VIVA-MIND study into a confirmatory Phase III study, and we will seek regulatory feedback of the FDA on this one. Then what is probably the news of the quarter is that we start managing and building the growth strategy of theVivoryon beyond VIVIAD in AD and in other indications. And I have a couple of charts on this one to be more specific. We want to become the leader in oral small glutaminyl cyclase inhibitor molecules and leverage our platform we have so far. And we want to go into these different molecules and different indications with a new focus on kidney function and chronic kidney disease and NASH, oncology and other biomarker-related indications in AD, more of that comes in the next chart. Finally, we are developing the company and organization steadily. And to do this, we are intensively communicating 2 investment banks. So we have a broader sell-side coverage achieved in the last quarter. We are still having a healthy cash position and maintain that, and we're very focused on this. So we can reach into the second half of 2024. And then there is another news, which is that Florida Schmid has decided not to renew this contract with Vivoryon and therefore, we'll phase out effectively on the 1st of March 2024. And Doering, who has currently the position of Investor Relations and Strategy, will take over that position as Chief Financial Officer. And I will take the opportunity here to thank Florian deeply for the trustful and promising and always excellent collaboration and we had a very good time together at Vivoryon. And we worked diligently together, and I want to wish him all the best for his future plans and endeavors and congratulate him on the successes we had with the Vivoryon so far. Finally, we want to come back to what happened in the third quarter. So myself and Ann were elected to the company Board as Executive Directors, with a good majority of the roads and feel entrusted to continue to manage the company. Now, going to the next chart. And this is new information because the first time disclosed here, the total discontinuation rates of the VIVIAD study as a cutoff date of the 20th of November 2023. And we do this at this point in time because at that point in time, we have a comparable treatment duration, 2 other studies which have 72 and 76 weeks of treatment duration. And at the point of cut-off, we had 78 weeks. So probably we can a little bit compare what discontinuations overall are there. And, of course, our discontinuations we published here are blinded, so we don't know yet what is active in placebo. But if you take the blinded total discontinuation rates at that cutoff date, we stand at 12.7%. And you can compare that to the right to the lecanemab, on donanemab data, and you will see that our discontinuation rates are lower. And we can confirm also that within that discontinuation rates, you see that the small minority is the reason or adverse events. And they are also very low and very favorable compared to other treatments in early IB. So we think this is a very positive news for the reliability of the VIVIAD study and the profile of our [indiscernible] in the treatment of early Alzheimer's patients. Going to the next slide. This is also not a new information but more of a confirmation of that the planning and the execution of the VIVIAD study is performed very diligently. The low discontinuation rates are one part that confirms the statistical power of the study. The other part is, of course, the variability of the endpoints, and we have looked into that recently. And based on our analysis, we can confirm that the power of the study is above 80% as specified and assumed in the protocol to detect the treatment difference between active and placebo of Cohen’s d of 0.35. And this is probably a very comforting situation a couple of months before the readout. This study stays completely on track. The end of the treatment phase will be until the end of the year. This means the last patient having the last dose will be still this year. And then after the last dose, every patient has a minimum period of safety follow-up of 4 weeks. And then the study is terminated for those patients. And then we have, of course, a data cleaning period and statistical data and analysis and management period, and then we're going to release the data top line during the end of the first quarter of 2024, and we can confirm this. Switching from VIVIAD to VIVA-MIND, coming back to the recent DSMB decision, which is a quite important milestone to actually develop the study further towards the Phase IIb and Phase III. So we have now the same population, the same dose, the same drug in 2 parallel studies, which allows us to potentially confirm the positive VIVIAD results with the VIVA-MIND study. And just to your memory, the primary end point of the VIVA-MIND study is the clinical dementia rating scale, the CDR sum of boxes, which is an agreed and approved confirmatory endpoint for an early AD study by the FDA, and we have a significant number of key secondary and exploratory endpoints, which, from our point of view, would qualify that study as a Phase III study if we would adapt the sample size and going from the current power of 80%, probably to a power of 90% or 95%, meaning adding a couple of more patients. But there would be, from our point of view, no further design changes needed. And in order to verify this, we will have an end of Phase II meeting with the FDA after the VIVIAD results. Going to a little bit to the positioning now of our drug versus what is already there because we cannot be agnostic about the progress, which has already been done in early AD with the monoclonal antibodies having delivered positive Phase III data. And what you can see on this chart that for the assessment of the efficacy of drugs in early Alzheimer's disease, different scales are used. It's not only CDS boxes are used, other scales can also be used. And when you look in a broader context, you see also people going in co-primary endpoints. There's various ways to look at efficacy in Phase III. We have [indiscernible] in some of boxes in the VIVA-MIND as a potential confirmatory study, and we have, as an intermediate efficacy study endpoint looked at the CogState NTB and the VIVIAD study. And what you can see and what is probably important to know or to see is that lecanumab slows the progression about 27% using the CDS boxes endpoint. And donanemab has given us stratified results. And what you see here is that in the low medium tower patients, so patients which have very little cellular destructions in the neurons, the efficacy is about 35%, slowing down the profession, whereas in the combined population and combined means low medium town and the high power, it's 22% and it's significant. But if you only look at the high tower population, so patients who have already substantial cellular destruction in the neurons, the efficacy is only 6% in slowing disease progression, and it's not significant. In other words, monoclonal antibodies, of course, are efficacious in early Alzheimer's disease, but the adverse events of areas also concerned patients in the earlier status and in the slower progressing AD stages. And in the slightly more advanced and more progressive patients with a higher power levels. Monoclonal antibodies, at least lecanumab, hasn't shown significant efficacy and lecanumab hasn't yet provided that type of stratification to the public. In other words, we see a very good opportunity on the next chart about the remaining very high unmet medical needs in early AD despite the recent treatment successes of the monoclonal antibodies. Specifically, we see an opportunity in improved safety and absence of product-related RVs and no need of infusions in the very early mildly progressing AD patients, and we see an opportunity of more robust efficacy in the more progressive, more advanced mild AD patients who have elevated tau levels already. And we believe that varoglutamstat based on the mechanism of action, can become a first-line single-agent treatment in early AD for all this population and has distinct advantages in the various subsetting we have just discussed. And moving to the next chart, and not try to get misunderstood here, and it's very important. We do not deviate from varoglutamstat in early AD. That is our core and lead program, and we do everything to get this product to the market and targeting market authorization as soon as efficiently as possible and try to get that product to the patient. But moreover, we need to look beyond the BDA data and beyond early AD. And as we stay laser-focused in the clinic, we have some research resources now available and freed up from this program and can look at other areas where glutaminyl cyclase inhibitors can provide unique health benefits potentially. And, therefore, we do a couple of work stream or we have initiated a couple of work streams where we try to advance our pipeline contingent on media results. And that is that we look into renal disease by amanding the VIVIAD protocol into adding some biomarkers of renal turnover to see whether varoglutamstat as a QBTL inhibitor has an effect on renal turnover and on renal disease. And to your background, elderly patients, as we have in the VIVIAD study with an average age of 70 usually have a reduced glomerular filtration clearance, reduced cleaner function already. And we can see whether varoglutamstat effect that reduced [indiscernible]. We are also preparing second-generation glutaminyl cyclase inhibitors for Alzheimer's disease. And we try to explore additional indication with also new QPCT/L inhibitors from our platform. The goal is that we want to have 1 to 2 additional development programs with second-generation glutaminyl cyclase inhibitor, which are back up by our scientific expertise and existing synergistic pathways to existing programs. So we want to do it step-wise slowly diligent to build our pipeline after VIVIAD results. And on the next chart, we try to be a little bit more specific on this. So in Alzheimer's disease, we have and will map out opportunities for life cycle management, for example, to look into whether we should go in moderate Alzheimer's disease or we should look into going into asymptomatic patients in AD. These are options we will look at after the VIVIAD results, and we will be guided by this, but VIVIAD results. We also look at new small or second-generation glutaminyl cyclase inhibitor as fast followers of varoglutamstat with an improved profile. And the objective here is to build a small franchise in AD with new molecules and oral inhibitors of glutaminyl cyclase. And the discovery efforts have been initiated in the third quarter. We are going on, and we expect in 2024 after we VIVIAD results to give an update on this and potentially are lucky to nominate development programs. The next thing is on the right side is chronic Kinetis and this is new, and I have a specific chart on this, why that is interesting. We have in VIVIAD the unique opportunity to look at long-term effect in patients with a partially impaired kidney function as the elderlies do not have any more normal kidney functions in many subjects and to look at biomarkers of kidney function and see whether QPTC/L can change these kidney biomarkers. And there is strong pharmacological evidence that QPTC glutaminyl cyclase inhibitor should do this and they should reduce the inflammatory fibrotic process in the kidney, and I'll show you some example on the next chart. And also, for Cancer, NASH, CNS and other disorders, we are looking for second-generation specifically approved for the indication molecules to put this in the indication. And we have also made on the right side, which were more positioned in acute kidney injury and fibrosis. And we have model selector, small molecule inhibitors, where we look into proof-of-concept studies in animal models and try to move them forward. To be very clear, we do not think that we want to have 6 development programs out of that or 8, we do not want to be a huge company with a lot of development programs. We want to select 1 or 2 of those to move the most promising forward and to become successfully a biotech company with a broader portfolio, but not a huge portfolio. And going back to the kidney disease, we have two rationales to look into this probably as a first priority after Alzheimer. And that is there is new scientific foundation that inflammation and fibrotic pathway require pyroglutamization for full effect. So in order in order that the kidney has inflammation and fibrosis, it becomes worse. It needs pyroglutamization of some cytokines, specifically the CCA 2 cytokine and the factor keen cytokine, both for full efficacy to disturb the kidney function needs to be pyroglutamized. And we can, with our glutaminyl cyclase inhibitor, reduce or prevent this pyroglutamization and therefore, reduce inflammation and fibrosis. Additionally, we have here the opportunity, what you would say is a classical bet to bench reverse engineering situation where we can use biomarker for VIVIAD study to see whether the hypothesis that we can affect this inflammatory and fibotic pathways, we can already measure that in these patients, and that what we integrated now in the VIVIAD study. And so, this is a very cost-efficient and effective opportunity because we will have -- besides the scientific data, we were of also some data from patients out of our study. That allows us a comprehensive assessment of the opportunity in chronic kidney disease, of course, contingent of the VIVIAD results because the data will only be delivered in the VIVIAD study and after the final headline data of the VIVIAD study. And with that, I want to move forward to Florian to lead you through the financial results of the company. Thank you.

[Florian Schmid, executive]

Thank you, Frank. In the third quarter of 2023, we continue to advance our clinical studies forward and we remain well capitalized into the second half of 2024. Research and development expenses were EUR 10.5 -- sorry, EUR 10.4 million in the 9 months ended September 30, 2020, decreased by $5.6 million compared to the 9 months ended September 30, 2022. This decrease is primarily attributable to a EUR 3 million lower expenses related to our clinical trial VIVIAD and 2.6 million lower manufacturing costs for study drug production. General and administrative expenses of EUR 6.8 million for the 9 months ended September 30, 2023, increased by EUR 2.6 million compared to EUR 4.2 million in the 9 months ended September 30, 2022. The main reasons for the increase were EUR 0.9 million higher personnel costs, EUR 0.9 million higher costs for non-executive [indiscernible] and EUR 0.8 million higher consulting costs. The reason for the cost increases in personnel and non-executed board were predominantly caused by accelerated share option expenses and severance payments because of the 2023 board changes. As in previous periods, our finance result was predominantly driven by the FX result on our U.S. dollar cash and U.S. dollar receivable in our balance sheet. the general interest rate trend in the 9 months ended September 30, 2023, we also had some interest income of EUR 0.2 million from our fixed term deposits. While we could not generate any interest income from our liquid funds in the 9 months ended September 30, 2022. The income tax reported relates exclusively to deferred taxes that must be reported in accordance with IAS 12, but the company does not pay any taxes due to the existing loss carryforwards. All this together resulted in a net loss of the 9 months ended September 30, 2023, of EUR 17.1 million compared to EUR 18.9 million for the 9 months ended September 30, 2020. We are carefully and selectively spending until VIVIAD readouts during the end of the first quarter of 2024. On the next slide, I would like to highlight selected KPIs. The company held EUR 17.0 million in cash and cash equivalents as of September 30, 2023, plus a term deposit of EUR 16 million, which is disclosed under financial assets. Combining the cash equivalents and the term deposits, the Vivoryon has EUR 33.0 million in liquid funds at its disposal. This compares to our cash position of EUR 26.6 million as of December 31, 2022. On September 30, 2023, total assets amounted to EUR 4.6 million and total equity was EUR 37.0 million. As of September 30, 2023, the company's issued share capital increased to EUR 26,066,808, including the exercise of share options. Overall, our cash runway is into the second half of 2024. This guidance does not include any potential milestone payments from development partnerships, potential payments from licensing agreements and/or additional financing measures as exercise of the options granted in connection of the private placement announced on September 30, 2022. So I'd like to move to the next slide. And yes, ladies and gentlemen, please allow me just a few personal words. I'm looking forward to the months ahead of us as a joint management team before I move on to new challenges for purely personal reasons. I would like to take this opportunity to thoroughly thank my colleagues for their support in cooperation over the past 3 years. I'm leaving the company in solid financial footing as it approaches the VIVIAD readout during the end of the first quarter of 2024. I have every confidence in the expertise of my successor, Anne. She and I will work together seamlessly to ensure a smooth transition, and I'm happy to contribute as a strategic adviser after Eneus [Indiscernible] the CFO role. I trust that Annie, together with Frank in Mick will lead the entire Levorin team on their continued mission to ease the burden of all those affected by the devastating reality of Alzheimer's disease. And with that, I would like to turn the call over to Anne.

[Anne Doering, executive]

Thanks, Florian. I'm honored to assume the role of Chief Financial Officer at this pivotal period for Vivoryon . Since I've joined Vivoryon, Florian and I have worked closely on many financial initiatives for the company. With active exchange will continue over the coming months as we ensure a smooth transition of the CFO role. It's been a pleasure to work alongside the Vivoryon team this past year to support the company's strategic goals and position us for continued growth, and I'm thrilled to be a part of the team that has a real shot at bringing much needed hope and relief to all of those affected by Alzheimer's disease. Vivoryon approach is highly differentiated from all others in the field, and I will give it my all to help bring this unique medicine over the finish line. With our upcoming VIVIAD Phase IIb readout during the end of the first quarter of 2024, we're approaching a major inflection point, and I not be more excited to continue to support Vivoryon, along its promising future growth path. I look forward to working closely with Frank and Michael as we continue to drive the Vivoryon Therapeutics program forward and develop further research initiatives. I'm happy to share with you an overview of Vivoryon's recent key activities as well as future multiple value-generating catalysts and near-term events. We have a lot to look forward to, and we're well positioned to share several facets of our progress throughout 2024 and beyond. We hosted a successful virtual R&D event with key opinion leaders in October. These KOLs highlighted various pathology, clinical development strategy and the clinical applicability of the key endpoints in the VIVIAD study. We were very pleased to see a sell-side coverage initiated by several investment banks as we continue to make strides in increasing street awareness of Vivoryon. We have also had meaningful progress for both VIVIAD and VIVA-MIND with positive independent DSMB decision supporting the 600 milligram twice daily dose of varoglutamstat. For VIVIAD, we're on track to report final top line results during the end of the first quarter of 2024. And for VIVA-MIND, we're continuing recruitment at the 600-milligram dose, following the DSMB decision with 21 sites open across the U.S. With both studies advancing as planned, we continue to work towards an end of Phase II meeting with the FDA in the U.S. when we will leverage the VIVIAD data in our FDA discussions and future plans. Overall, we believe these developments point towards continued advancement of the company and value creation as we approach multiple key inflection points. Now, turning to our core asset. We have unique potential to address key hallmarks of AV and reduce the progression of cognitive decline in early AD patients by focusing on NPE A-beta biology with varoglutamstat. We believe that with varoglutamstat favorable safety profile, ease of administration and strong signs of efficacy and synaptic improvements, we are uniquely positioned to bring a highly differentiated, potentially first-line single-agent therapeutic options to patients with early AD. With Vivoryon results in hand, we will be able to answer key questions regarding future opportunities in AD, particularly potential expansion of our target patient population to capture asymptomatic and moderate AD patients. Potential combination studies with antibodies in AD as well as applications and additional indications. There are also development opportunities with our partner sincere in Greater China. Vivoryon has had an active quarter with substantial progress towards major milestones. We believe we have a bright future ahead of us with our core asset varoglutamstat, and we are well positioned to be a leader in QPCT/L approaches for early AD. However, we don't want to stop there. We see future opportunities to develop our leadership position in AD and also go beyond this with our early-stage research initiatives designed to address a wide range of indications with high unmet medical needs. And with that, we'll now open the call to take questions. Thank you.

[Operator]

Now, we'll begin the question-and-answer session. [Operator Instructions]. Just give us a moment. And it comes from line of Lucy Codrington from Jefferies. [Operator Instructions].

[Lucy-Emma Codrington-Bartlett, analyst]

Just to start with, you mentioned in the presentation that you would aim to convert VIVA-MIND to a Phase III in the event of a positive VIVIAD readout. I just wanted to confirm, though, would you still need to complete at least the Phase IIa portion, if not the Phase IIb? And do we have any insight into the timing of that Phase IIa data way to continue as normal? And I think, Anne, you may just clarify my second question because the wording on the press release is recruitment is ongoing in the second dose cohort of VIVA-MIND. But just confirming that all patients being recruited now are on 600 milligrams. And did any patients actually start on the 300-milligram cohort before you got that okay from the DSMB. And then just how that trial -- any update on how that trial is recruiting and I'll stop there. I'll jump back in the queue.

[Frank Weber, executive]

So let's start with the end. Of course, there have been patients already recruited in the second cohort because we don't stop the recruitment once the first quarter is over, we continue. But with the DSMB decisions, patients in the second cohort, which have been allocated to 300 milligram in the active arms to placebo and placebo [indiscernible] placebo and in the serum arm, they now get moved to the 600 milligram. So they get up titrated. And of course, that has been preplanned. There are study medication kits in place and everybody gets in a blinded way onto the 600-milligram dose. So these -- there are some patients who have been for a couple of weeks or months being exposed to 300, which will be now switched to 600. And all your patients will go then to the 600 directly. Did that answer the second part of your question?

[Lucy-Emma Codrington-Bartlett, analyst]

Yes. okay.

[Frank Weber, executive]

So then the question on how VIVA-MIND will evolve from to a IIa to IIb to Phase III. And this has been always an adaptive design study with the idea in mind that it can serve as a confirmatory Phase III study if VIVIAD delivers positive results. And that's not a new information that has always been the case. Now the question is, will there be a stop in recruitment between Phase IIa/IIb No, there will not be. We continue seamlessly recruitment between IIa, IIb and then Phase III. The Phase III change in amendment of the study is, of course, contingent on 2 major milestones. One is VIVIAD is positive. And one is that we have an agreement with the FDA to do so in a similar way. But in all honesty, we are a little bit stealing here from Lilly, who has changed the trial laser study to -- in a much more radical way than we're going to plan to change the VIVA-MIND study and convert it into a Phase III study. So it is not an unheard or never done in early AD that you manned the study and upgrade it from a Phase II and the Phase III. So we are following, I would say, established principles in early Alzheimer's disease. Whether we still would do a futility analysis after positive VIVIAD data and how that looks like is a matter of debate, but if VIVIAD is positive with futility analysis is probably only a tick box to be done because it's based on the EEG parameter and a non-worsening in cognition. So if VIVIAD show the benefit in cognition in EG, probably we can easily tick box that transition from Phase IIa to IIb. Did that answer your question, also?

[Lucy-Emma Codrington-Bartlett, analyst]

Yes. I guess I do -- I appreciate that there are trials that are converted from Phase II to Phase III. This isn't a new thing. It's just whether you'd still need -- given you've got the different endpoints in the Phase IIa then the Phase IIb portion, whether you still need to step through those before doing that convergence to questions I get that

[Frank Weber, executive]

Sorry, there is probably a good that you asked that question. To be very clear, the primary endpoint of the study for efficacy is always the series of boxes. What we have put in into the VIVIAD study is a futility analysis because in the absence of VIVIAD, if you look at each study alone, each study initially needs to stand alone, and it initially needs to make a sense on itself. We did not want to recruit 400, 500 patients without hitting any [indiscernible] and the problems which arose there that we base with futility analysis on a positive effect on the Theta power in the EEG. So we need a pharmacological engagement [indiscernible] positive after 180 patients completed for 6 months. And that is also a parameter we are measuring, of course, VIVIAD. The second thing and the second part of the futility analysis is that we have no worsening in the varoglutamstat arm versus the placebo arm because we don't want to do harm to the patient in terms of cognition. We do not require positive cognitive effect at futility because that is probably too much asked for. So the thing is that we have, I think, the ABC score as the parameter defined to show a non-worsening of completion. And in these 2 parameters are met for futility, the study progresses, but the primary endpoint always stays a some of boxes. And the primary endpoint is not involved in the futility analysis

[Operator]

Now we're going to take our next question. Just give us a moment. And the next question comes from the line of Joseph Hedden from Rx Securities.

[Joseph Hedden, analyst]

You give another update on 20th November on safety. Can you confirm still whether you see no incidence of ARIA adverse events at that time? And then secondly, just a [indiscernible].

[Frank Weber, executive]

Yes. We do not see any signs of [indiscernible]. We have not seen a single sweet with a preferred term or a in-term or whatever you can think of an ARIA.

[Joseph Hedden, analyst]

Great. That's very good to know. And then secondly, you've mentioned in ones and also previously about the accelerated titration to get to the 600 mg dose that patients are getting in vitamins that obviously, they didn't get in VIVIAD, this is something that will come into patients and media further down the line, hopefully. So are all new patients now getting that? Or is there still some things that need to be done before you implement that in VIVA-MIND?

[Frank Weber, executive]

No, in VIV-MIND, everybody gets the accelerated titration or already got it in the first 8 cohort, and that was the basis of the DSMB decision. So from patient 1, everybody started with 150 milligram twice daily. After 4 weeks went to 300 milligram twice daily and at week 9 -- so after another 4 weeks, we started the 600 milligram twice daily. The advantage is that you have start with higher dose and have more easy pharmaceutical formulation and so on. So VIVIAD is a little lower, VIVA-MIND is faster in the titration and probably you don't need a starter pack in the future. But it happened from patient 1 onwards, and it will continue like this now because it was cleared from the DSMB for safety and tolerance being adequate to treat these analgetic patients. And I can confirm, we, of course, looked also whether the safety profile and the blinded way of VIVIAD and VIVA-MIND is comparable or there are differences. And we cannot see differences between VIVIAD and VIVA-MIND, which are in any way pointing to that faster titration regime would put any additional risk to the patient. So we are pretty certain that works very well for the patient as well.

[Joseph Hedden, analyst]

Okay. That's great. And then just finally, on Chinese development [indiscernible], has there been any news from them about the Phase I start it's just -- it seems that CTA has been approved quite a long time now. And are they just waiting on the readout of VIVIAD before they pull the trigger and starting the trial?

[Michael Schaeffer, executive]

Yes. Joe, it's Michael. Nice talking to you. I'll give you some updates here on the -- in situational questions. So actually, what you said is a little bit -- needs to be a little bit changed, if you will, because the CTA approval, yes, you're right. It's around since quite a while. But you also remember that we had a change in the planning of the Chinese trial, let's say, how this portion is incorporated in the overall strategy, which resulted in a switch from the earlier plans to even included into the VIVIAD study towards the VIVA-MIND study. So -- and this has -- the result actually that sincere needed to amend and added some of their, let's say, regulatory paperwork they need to do in China. And actually, the last green light, which was important so that they can start no clinical development, they just received that in September -- mid of September this year. So that's why also you might think there's not much activity, but be assured that we are in constant contact and negotiations with them. In the end, of course, it's their call when they will start the Chinese development. So that's not our call. But again, there is -- so it's not silent on our end. It's -- we are in close connection here.

[Joseph Hedden, analyst]

Okay. That's great.. Thanks, Michael, and thanks, Frank.

[Operator]

Thank you. [Operator Instructions]. Now we're going to take our next question, and it comes from the line of Luis Morgado from Vanlose Kampen.

[Luis Morgado, analyst]

I have a few questions. Maybe to start off with varoglutamstat. Could you expand a bit more on what is this end of Phase II meeting with the FDA? So will you look at both efficacy and safety from VIVIAD? And also, will you at this point, decide whether to adapt to the U.S. trial into a Phase III?

[Frank Weber, executive]

Well, this is -- this end of Phase II meetings are pretty standard. You have your draft clinical report, you have your development strategy, you develop a briefing book based on this. And then you asked the FDA key questions about the further development strategy to the market and the collected evidence so far. And of course, if VIVIAD is positive, we will make the claim of substantial evidence of effectiveness in the VIVIAD study to treat early AD based on the intermediate clinical endpoint. And I think it's really good that you ask this question because our development strategy actually has -- on the beginning in business opportunity to try to get an accelerated approval at that point in time agreed with the FDA. For doing so, you need either to show substantial evidence of effectiveness. [Technical Difficulty]. So that is a pretty standard procedure for the end of Phase II meeting. This is a typical meeting you can have with the FDA, you have with the FDA to agree on a further development step and the process to the market. And it will include efficacy and safety of VIVIAD and all prior programs and actually also the non-clinical data we have collected so far. So it's a pretty big meeting package, which includes everything on varoglutamstat haven't completed so far and all the ideas we have for its future.

[Luis Morgado, analyst]

Okay. Very clear. And maybe moving on a bit to the additional development programs that you talked quite a lot today. So when do you actually amend the protocol of VIVIAD to include the assessment on renal disease? And will you also share data on this the readout at the end of Q1? And maybe if you can already provide some guidance on when will we hear more on which are the selected indications?

[Frank Weber, executive]

So good question. Submission is done, already completed signed and should be done or it's done these days. So it's done or it's on its way or done or signed. So it's a process. That's the first thing. The second thing is these are partially biomarker data and biomarker data require, of course, analytics, and these analytics will happen after the unlining of the study. So when we publish the top line data, during the end of the first quarter. These data will not be yet ready for communication. That will happen at a little bit a later point in time. I cannot really tell you exactly when because we still need to book the lab time and space at certain laboratories to conduct this analysis and then, of course, need to calculate the time from there on to conduct the statistics. And -- but it will be definitely during the second quarter of 2024. So we will not have a huge delay, but it will not be upfront. Yes, let -- did that answer that question? And then the third question is about the prioritization of indication and molecules. And what I can -- what is important to know is that we started these research activities in the third quarter in order to come to a scientific-based evidence-based decision which indications and which molecules we will prioritize. And we do not see ourselves in announcing suddenly 4 or 5 new development programs and molecules. I think that will be over then, and that doesn't make really a sense. What we want to do is to select the most promising and the most diligent and the most advanced based programs moving forward. Of course, if the clinical data from VIVIAD on kidney would support a development in kidney, that probably would be -- have the second priority after establishing all the Alzheimer's franchise. So first comes Alzheimer's and a fast follower and a second molecule in Alzheimer because that is our core expertise. And then we need to make choices from from other indication opportunities, the one with kidney is so interesting because we can have clinical data already from VIVIAD to support the evidence of the mechanism of action in that indication, which, of course, when we look into net oncology or let us say, down subjects with no syndrome or Huntington's or other disorders like Parkinson's where glutaminyl cyclase inhibition may play a role. We have scientific data, but we do not have clinical data, we would need to generate that. So if we have clinical evidence for kidney, that would support giving that a second priority. And then we go further in assessing our scientific data and the scientific data of others and the molecule properties also we will select what fits where best for probably another program. Is that a sufficient answer? Or do you have another question on that?

[Luis Morgado, analyst]

No. That is all for me. That was quite clear. So thank you for the question.

[Operator]

[Operator Instructions]. Give us a moment. And the next question comes from the line of Alexander Galitsa HAIB.

[Aliaksandr Halitsa, analyst]

I'm just wondering how do you think about the outline those auxiliary programs that you are preparing to initiate or initiating? I'm just wondering how do you think about the financing those? Should that be -- well, are you looking into development partnership? Or should that were you rather leading towards a capital raise on the type of, hopefully, positive VIVIAD results. So just some color how do you think about financing?

[Frank Weber, executive]

What? Say again what the cost of covering what -- the new monitors that you were set

[Aliaksandr Halitsa, analyst]

The new indications that you outlined, how do you think about financing those programs?

[Frank Weber, executive]

I mean, we have all opportunities open with positive VIVIAD results. And I think I try to say that it is, of course, contingent on VIVIAD results. In terms, meaning that VIVIAD results will guide also the way we're going to develop our pipeline. And if VIVIAD is clearly positive, fast followers of early Alzheimer's disease become a priority. And with VIVIAD being positive, clearly, I think we have no limitation of financing the company in all potential ways, including the follow-up programs. The -- the other thing is if we have evidence for kidney disease in VIVIAD and suitable molecules and a good development pathway. I don't think there is issues of finding money in all of the potential pathways. You know we have a cash reach into the second half. But of course, these development programs would take much longer than the second half. So there will be money inflow in the company based on positive VIVIAD results, but there is various options to do this, and that not needs to be an open market that can be collaboration that can be any type of yes, additional money we can raise. So -- and I think we cannot be more specific on this even you like to do because it's really contingent on how VIVIAD looks like.

[Aliaksandr Halitsa, analyst]

Understood. And then one question on VIVIAD. Can you remind me whether you differentiate between low, medium and high tau patient population in VIVIAD?

[Frank Weber, executive]

Yes. We have also different from other studies. We have a mandatory tau measure and inclusion criteria into the trial. So all our patients are to positive based on the CSF sample we take at the baseline. And we will basically stratify the population prospectively by the media and the median of how we published Phospho-tau is 33, I think, the median. So we look at patients with a phospho-tau level below and above the median of -- in our study. But different from other studies, we do not have really no tau patients because when you look, for example, in the [indiscernible], there was no including criteria on tau. Of course, patients who qualify based on CSF had tau assessments, but patients who qualified in the [indiscernible] study based on PET data, they didn't have a tau level, at least to my knowledge. And so -- and really stratified, but they had no particularly minimum tau threshold as far as I know, in the study to be included. They had initially a high-tau exclusion criteria, but they skipped that after, I think, 250 patients in their study with all the amendments that did in the study. So I think we are the only study who has a stringent tau-positive the study, and all our patients are tau positive, and we basically stratified by the median of the tau patients.

[Operator]

There are no further questions for today. I would now like to hand the conference over to our speakers for any closing remarks.

[Frank Weber, executive]

Yes. I thank you for attending the third quarter call. You may have observed that it is probably the first quarter call we did. So we try to frequently do now these calls and with each quarter, not only have a press release by a call. And then with that, I want to thank you for your attention. And yes, I wish you all the best for the Christmas period, and hope to hear from you soon. Goodbye.

[Operator]

Thank you for participating. You may now all disconnect. Have a nice day.