Good day, and thank you for standing by. Welcome to the Vivoryon Therapeutics third quarter results 2023 earnings call. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be the question- and- answer session. To ask a question during the session, you need to press star one one on your telephone keypad. You will then hear an automatic message advising your hand is raised. To withdraw your question, please press star one one again. 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, 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's Chief Executive Officer, Frank Weber, and Florian Schmid, our Chief Financial Officer. Also with us on today's call and available for questions is Michael Schaeffer, our Chief Business Officer. We will begin today's call with opening remarks from Frank on Vivoryon's 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.
Yeah.
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 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, ensuing 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.
Thank you, Anne. Thank you, Nadia. Good afternoon, good morning, everybody. Let's go into the activities of Vivoryon. Vivoryon is actually defined by three 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 three main areas. So our approach is stopping the production of neurotoxic pyroglutamate-beta 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 ARIAs, we do not have imaging needs, and that reduces cost and efficiency of the treatment. Finally, the market is very significant with a very high unmet medical need. There are millions of people waiting for efficient and well-tolerated therapies. Our approach is phase II studies 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 2024, confirming what we have said before.
And then we have the American VIVA-MIND study, where a recent DSMB decision allows to continue with the 600 mg twice-daily dose, which is exactly the same dose as we use in VIVIAD, just with a slightly faster titration regimen. And finally, the team and the people working at Vivoryon have a strong discovery, development, and management background, having brought 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 glutaminyl cyclase 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 this study is above 80%, which confirms the design of the study. We 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, yeah, relieved.
I would also say that with the 600 mg 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 glutamstat as we give it today. The adaptive design a positive DSMB decision , support potential expanssion to phase III and I need to be a little bit specific on this. In case VIVIAD study is positive, we have the intention 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 the Vivoryon beyond VIVIAD in AD and in other indications.
I have a couple of charts on this one to be more specific. We want to become the leader in oral small-molecule glutaminyl cyclase inhibitor molecules, and leverage our platform we have so far. We want to go into with 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 charts. Finally, we are developing the company and organization steadily. To do this, we are intensively communicating to 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 are very focused on this so we can reach into the second half of 2024.
Then there is another news, which is that Florian Schmid has decided not to renew his contract with Vivoryon, and therefore will phase out effectively on the March 1st, 2024. Anne Doering, who has currently the position of Investor Relations & Strategy, will take over that position as Chief Financial Officer. I will take the opportunity here to thank Florian deeply for the trustful and promising and always excellent collaboration. 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 he had with Vivoryon so far. Finally, we want to come back to what happened in third quarter.
So myself and Anne were elected to the company board as executive directors with a good majority of the votes and feel entrusted to continue to manage the company. Now, going to the next chart, and this is new information because we first time disclose here the total discontinuation rates of the VIVIAD study as a cutoff date of the twentieth of November, 2023. And we do this at this point in time, because at that point in time, we have a comparable treatment duration to other studies which have 72 and 76 weeks of treatment duration, and at the point of cutoff, we had 78 weeks. So probably we can a little bit compare what discontinuations overall are there.
Now, of course, our discontinuations we publish here are blinded, so we don't know yet what is active or placebo. But if you take the blinded total discontinuation rate at that cutoff date, we stand at 12.7%, and you can compare that to the right, to the lecanemab and 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 a small minority is the reason are adverse events, and they are also very low and very favorable, compared to other treatments in early AD. So, we think this is a very positive news, for the reliability of the VIVIAD study and the profile of our varoglutamstat in the treatment of early Alzheimer's patients. Going to the next slide.
This is also not a new information, but more 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 then assumed in the protocol, to detect the treatment difference between active and placebo of a Cohen's d of 0.35. And this is probably a very comforting situation a couple of months before the result. The 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 four weeks, and then the study is terminated for those patients. And then we have, of course, a data cleaning period and a statistical data and analysis and management period. And then we're gonna release the data top line during the end of the first quarter 2024, and we confirm-- 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 phase IIb and phase III.
So we have now the same population, the same dose, the same drug in two parallel studies, which allows us to potentially confirm the positive VIVIAD results with the VIVA-MIND study. Just to your memory, the primary endpoint of the VIVA-MIND study is the Clinical Dementia Rating scale, the CDR-SB, which is an agreed and approved confirmatory endpoint for an early AD study by the FDA. We have a significant number of key secondary and exploratory endpoints, which, from our point phase III study, if we would adapt the sample size and going from a 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 phase II meeting with the FDA after the VIVA-MIND 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 early AD with monoclonal antibodies having delivered postiove in early 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 CDR-SB 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 is, there is various ways to look at efficacy in phase III.
We have chosen the CDR-SB in the VIVA-MIND, as a potentially confirmatory study, and we have, as an intermediate efficacy study endpoint, looked at the Cogstate NTB in the VIVIAD study. What you can see and what is probably important to know or to see is that lecanemab slows the progression about 27% using the CDR-SB endpoint, and donanemab has given us stratified results. What you see here is that in the low, medium tau patients, so patients which have very little cellular destructions in the neurons, the efficacy is about 35%, slowing down the progression. Whereas in the combined population, and combined means low, medium tau and the high tau, it's 22, and it's significant.
But if you only look at the high tau 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 ARIAs also concern patients in the earlier stages and in the slower progressing AD stages. And in the slightly more advanced and more progressive patients with a higher tau levels, monoclonal antibodies, at least donanemab, hasn't shown statistically significant efficacy, and lecanemab 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 need 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 ARIAs 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 sub settings we have just discussed. And moving to the next chart, and not try to get misunderstood here, and this is 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, as efficiently as possible, and try to get that product to the patient. But moreover, we need to look beyond the VIVIAD 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 VIVIAD results.
And that is that we look into renal disease by amending the VIVIAD protocol into adding some biomarkers of renal turnover to see whether varoglutamstat, as a QPCTL 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, so a reduced renal function already, and we can see whether varoglutamstat affects that reduced renal function in the elderly. Excuse me. We are also preparing second generation glutaminyl cyclase inhibitors for Alzheimer's disease, and we try to explore additional indication with also new QPCTL inhibitors from our platform.
The goal is that we want to have one to two additional development programs with second generation glutaminyl cyclase inhibitor, which are backed up by our scientific expertise and, existing synergistic pathways to existing programs. So we want to do it stepwise, 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, by the VIVIAD results.
We also look at new, small, oral, second generation, glutaminyl cyclase inhibitor as fast followers of varoglutamstat, with an improved profile. The objective here is to build a small franchise in AD with new molecules and oral inhibitors of glutaminyl cyclase. The discovery efforts have been initiated in the third quarter. We are going on, and we expect in 2024, after 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 kidney disease, 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 partially impaired kidney function, as the elderlies do not have any more normal kidney functions in many subjects.
To look at biomarkers of kidney function and see whether QPCT inhibitors can change these kidney biomarkers. There is strong pharmacological evidence that QPCT inhibitors or glutaminyl cyclase inhibitor should do this, and they should reduce the inflammatory and fibrotic processes of the kidney, and I'll show you some example on the next chart. 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. We have also meprin on the right side, which we more position in acute kidney injury and fibrosis. We have novel selective small molecule inhibitors, where we look into proof of concept studies and animal models and try to move them forward.
To be very clear, we do not think that we want to have six development programs out of that or eight. We do not want to be a huge company with a lot of development programs. We want to select one or two 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's. And that is, there is new scientific foundation that inflammation and fibrotic pathway require pyroglutamization for full effect. In order that the kidney has inflammation and fibrosis, it becomes worse, it needs pyroglutamization of some cytokines, specifically the CCL2 cytokine and the fractalkine 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 bed-to-bench reverse engineering situation, where we can use biomarker from VIVIAD study to see whether the hypothesis that we can affect this inflammatory and fibrotic pathways. We can already measure that in these patients, and that will be integrated now in the VIVIAD study. So this is a very cost-efficient and effective opportunity because we will have, besides the scientific data, we will have 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 on 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.
Thank you, Frank. Sorry. In the third quarter of 2023, we continued to advance our clinical studies forward, and we remain well capitalized into the second half of 2024. Research and development expenses were EUR 10.4 million in the nine months ended September 30, 2023. Decreased by EUR 5.6 million compared to the nine months ended September 30, 2022. This decrease is primarily attributable to EUR 3 million lower expenses related to our clinical trial, VIVIAD, and EUR 2.6 million lower manufacturing costs for study drug production. General and administrative expenses of EUR 6.8 million for the nine months ended September 30, 2023, increased by EUR 2.6 million, compared to EUR 4.2 million in the nine 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 board, and EUR 0.8 million higher consulting costs. The reason for the cost increases in personnel and non-executive 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. Due to the general interest rate trend in the nine 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 nine 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 existing loss carryforwards. All this together resulted in a net loss of the nine months ended September 30, 2023, of EUR 17.1 million, compared to EUR 18.9 million for the nine months ended September 30, 2022. We are carefully and selectively spending until VIVIAD readouts, until VIVIAD reads out 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, 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 40.6 million, and total equity was EUR 37.60 million. As of September 30, 2023, the company's issued share capital increased to EUR 26,066,008, 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 with the private placement announced on September 30, 2022.
I'd like to move to the next slide. Yeah, 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 and cooperation over the past three 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 advisor after Anne assumes the CFO role.
I trust that Anne, together with Frank and Nick, will lead the entire Vivoryon team on their continued mission to ease the burden of all those affected by the devastating reality of Alzheimer's disease. With that, I would like to turn the call over to Anne.
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. This 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 those affected by Alzheimer's disease. Vivoryon's 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.
phase IIb readout during the end of the first quarter of 2024, we're approaching a major inflection point, and I could 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 varoglutamstat 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 varoglutamstat pathology, clinical development strategy, and the clinical applicability of the key endpoints in the VIVIAD study.
We were very pleased to see 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 decisions supporting the 600 mg 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 mg dose following the DSMB decision, with 21 sites open across the U.S. With both studies advancing as planned, we end-of-phase II meeting with the FDA in the U.S., when we will leverage VIVA-MIND, VIVIAD data in our FDA discussions and future planning.
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 AD and reduce the progression of cognitive decline in early AD patients by focusing on N3pE-Abeta biology with varoglutamstat. We believe that with varoglutamstat's favorable safety profile, ease of administration, and strong signs of efficacy and synaptic improvement, we are uniquely positioned to bring a highly differentiated, potentially first-line single-agent therapeutic option to patients with early AD. With VIVIAD 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 and AD, as well as applications and additional indications.
There are also development opportunities with our partner, Simcere, 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 QPCTL 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. With that, we'll now open the call to take questions. Thank you.
Thank you, dear participants. Now, we will now begin the question- and- answer session. If you wish to ask a question, please press star one one on your telephone keypad and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by, we'll compile the Q&A roster. This will take a few moments. Now we're going to take our first question. Just give us a moment. And it comes from line of Lucy Codrington from Jefferies. So line is open, please ask your question.
Hi, thanks for taking my questions. Just to start with, you mentioned in the presentation that you had aimed 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 phase IIb? and do we have any insight phase IIa data, were you to continue as normal? And I think, Anne, you may just clarify my second question, because the wording on the press release says, "Recruitment is ongoing in the second dose cohort of VIVA-MIND." But just confirming that all patients being recruited now are on 600 mg.
Did any patients actually start on the 300 mg 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.
So, 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 cohort is over, we continue. But with the DSMB decisions, patients in the second cohort, which have been allocated to 300 mg in the active arm, into placebo, in placebo, they stay on placebo, and in the 300 mg arm, they now get moved to the 600 mg, so they get uptitrated. And of course, that has been preplanned. There are study medication kits in place, and everybody gets, in a blinded way, onto the 600 mg dose.
There are some patients who have been for a couple of weeks or months being exposed to 300, which will now be switched to 600, and all new patients will go then to the 600 directly. Did that answer the second part of your question?
Yeah, that's right.
Yeah. So, then the question on how VIVA-MIND will evolve from IIa to IIb to phase III. and this has been always an adaptive design study with the idea in 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 phase IIa to IIb? no, there will not be. We continue seamlessly recruitment between IIa, IIb and then phase III. The phase III change and amendment of the study is, of course, contingent on two 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 TRAILBLAZER-ALZ 2 in a much more radical way than we're going to plan to change phase III study. so it is not an unheard or never done in early AD that you amend 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, the 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 shows a benefit in cognition and EEG, probably we can easily phase IIa to IIb. did that answer your question also?
... Yeah, I guess I appreciate that phase III. this isn't a new thing. it's just whether you'd still need, given you've got phase IIb portion, whether you'd still need to step through those before doing that conversion of those questions, I guess, that's the
There are no different endpoints. Yeah. Sorry. It is probably good that you asked that question. To be really clear, the primary endpoint of the study for efficacy is always the CDR-SB. What we have put into the VIVA-MIND 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 decision on itself. We did not want to recruit 400 or 500 patients without having any from [audio distortion]
Futility as- [audio distortion]
The learnings up and the problems which arose there, that we base the futility analysis on a positive effect on the theta power in the EEG. So we need a pharmacological engagement parameter positive after 180 patients completed for six months. And that is also a parameter we are measuring, of course, in 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 cognition.
If these two parameters are met for futility, the study progresses, but the primary endpoint always stays CDR-SB, and the primary endpoint is not involved with the futility analysis.
Okay.
Okay, good.
Thank you. Now we're going to take our next question. Just give us a moment. The next question comes from the line of Joseph Hedden from Rx Securities. Your line is open. Please ask your question.
Good afternoon. Thanks for taking my question. You've given an update as of November 20 on safety. Can you confirm still whether you've seen no incidents of ARIA adverse events at that time? And then secondly, just-
This is easy to answer, Joseph. Yes. We do not see any signs of ARIA. We have not seen a single adverse event with a preferred term or a hidden term or whatever you can think of, of an ARIA.
Great. That's very good to know. And then secondly, you've mentioned in the release and also previously about the accelerated titration to get to the 600 mg dose that patients are getting in VIVA-MIND, that obviously they didn't get in VIVIAD, and this is something that will come into patient convenience 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?
No, in VIVA-MIND, everybody gets the accelerated titration or already got it in the first A cohort, and that was the basis of the DSMB decision. So from patient one, everybody started with 150 mg twice daily. After four weeks, went to 300 mg twice daily, and at week nine, so after another four weeks, they started the 600 mg 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 slower. VIVA-MIND is faster in the titration, and probably you don't need a starter pack in the future, but it happened from patient one onwards, and it will continue like this now because it was cleared from the DSMB for safety and tolerance being adequate to treat these elderly geriatric patients.
I can confirm, we of course looked also whether the safety profile in the blinded way of VIVIAD and VIVA-MIND is comparable or there are differences. We cannot see differences between VIVIAD and VIVA-MIND, which are in any way pointing to that the faster titration regime would put any additional risk to the patient. So we are pretty, pretty certain that that works very well for the patient as well.
Okay, that's great. Thanks for clearing that up. And then just finally, on Chinese development and Simcere, has there been any news from them phase I start? it's just it seems the CTA has been approved quite a long time now. And are they just waiting on the readout of VIVIAD before they pull the trigger on starting the trial?
Yeah. Hi, Joseph. That's Michael. Nice talking to you. I give you some updates here on the Simcere situational question. 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 resides in a switch from the earlier plans to even reinclude it into the VIVIAD study towards the VIVA-MIND study.
So, and this has the result actually that Simcere needed to amend and edit 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, you know, clinical development, they just received that in September, mid-September, this year. So that's why, also, you know, 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, you know, 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, yeah.
Okay, that's great. Very clear. Thanks, Michael, and thanks, Frank.
You're welcome.
Thank you. Dear participants, as a reminder, if you wish to ask a question, please press star one, one on your telephone keypad. Now we're going to take our next question, and it comes from the line of Luísa Morgado from Van Lanschot Kempen. Your line is open, please ask your question.
Hi, team. Yeah, I have a few questions. Maybe to start off with varoglutamstat. Could you expand a bit more on 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 the us trial into a phase III?
Well, 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 ask the FDA key, 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, from the beginning, inbuilt this 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. [audio distortion] 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 the further development step and the time, 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, pretty big meeting package, which includes everything on varoglutamstat having completed so far and all the ideas we have for its future.
Okay, very clear. And maybe moving on a bit to the additional development programs that you talked quite a lot today. So when did you actually amend the protocol of VIVIAD to include the assessment on renal disease? And will you also share data on this at the readouts 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?
So, good question. Submission is done, already completed, signed, and should be done or is done these days. So, it's done, or it's, yeah, 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 unblinding 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 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. But it will be definitely during the second quarter, 2024. So we will not have a huge delay, but it will not be upfront. Yeah, that's— Did that answer that question? And then-
Yeah.
Yes?
Oh, yes. Yes.
Yeah.
Yes.
Good. And then the third question is about the prioritization of indication and molecules. And 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 four or five new development programs and molecules. I think that will be overdone, and that doesn't make really sense. What we want to do is to select the most promising, and the most diligent, and the most evidence-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 an early Alzheimer franchise.
So first comes Alzheimer 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 action, in that indication. Which, of course, when we look into NASH oncology or let us say, down, subjects with Down syndrome or Huntington's, or other disorders like Parkinson's, where glutaminyl cyclase inhibition may play a role. We, we have scientific data, but we do not have clinical data. We would need to generate that.
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 the sufficient answer, or do you have another question on that?
No, that is all for me. That was quite clear. So thank you for taking my questions.
Thank you for the question.
Thank you. Dear participants, as a reminder, if you wish to ask a question, please press star one one on your telephone keypad. Now we're going to take our next question. Just give us a moment. The next question comes to the line of Alexander Galitsa from HAIB. Your line is open. Please ask your question.
Yes, good afternoon. Thank you for taking the question. I'm just wondering, how do you think about you outline those auxiliary programs that you are preparing to initiate or initiating? I'm just wondering, how do you think about financing those? Should that be or are you looking into development partnership, or should that or you'll rather leaning towards a capital raise on the back of hopefully positive VIVIAD results? So just some color, how do you think about financing?
Say that again, what, what the cost of covering what? The new molecules, the new research?
The new indications that you outlined, how do you think about the financing those programs?
I mean, we have all opportunities open with positive VIVIAD results, and I think I tried to say that it is of course contingent on VIVIAD results. In terms, meaning that VIVIAD results will guide also the way we're gonna 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 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 are various options to do this, and that does not need to be in the open market. That can be collaboration, that can be any type of 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.
Understood. Then one question on VIVIAD. Can you remind me whether you differentiate between low, medium, and high tau load patient population in VIVIAD?
Yeah, we have also different from other studies, we have a mandatory tau measure and inclusion criteria into the trial. So all our patients are tau positive based on the CSF sample we take at the baseline. And we will basically stratify the population prospectively by the median, and the median of tau 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 lecanemab, there was no inclusion criteria on tau.
Of course, patients who qualified based on CSF criteria had tau assessments, but patients who qualified in the lecanemab study based on PET data, they didn't have a tau level, at least to my knowledge. And, so, Lilly stratified, but they had no particularly minimum tau threshold, as far as I know, in that 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 they did in the study. So I think we are the only study who has a stringent tau positive criterion in the study, and all our patients are tau positive, and we basically stratify by the median of the tau level.
Thank you.
Thank you. That are all further questions for today. I would now like to hand the conference over to our speakers for any closing remarks.
Oh, yeah. I, I thank you for attending this third quarter call. You may have observed that it is probably the first third quarter call we did. So we try to frequently do now these calls and with each quarter, not only have a press release, but a call. And then, with that, I want to thank you for your attention and yeah, I wish you all the best for the Christmas period, and hope to hear from you soon. Goodbye.
That does conclude our conference for today. Thank you for participating. You may now all disconnect. Have a nice day.