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

Ladies and gentlemen, thank you for standing by. Welcome, and thank you for joining the Vivoryon Therapeutics Q3 Results 2022 Conference Call. [Operator Instructions] I would now like to turn the conference over to Manuela. Please go ahead.

Thank you, Timo. Good afternoon, and thank you for joining us today for Vivoryon's conference call to discuss the company's third quarter 2022 results and operational progress to date. This morning, Vivoryon issued a press release reporting its third quarter 2022 results, which is posted on the company's website at www.vivoryon.com. On the call with me today are Ulrich Dauer, Chief Executive Officer of Vivoryon; as well as Florian Schmid, our Chief Financial Officer; and Michael Schaeffer, our Chief Business Officer, who will be available for questions. We will begin today's call with opening remarks from Ulrich on Vivoryon's approach to overcoming the challenges of AD drug development, our strategic focus and progress and a review of the financial results for the third quarter of 2022. Following the prepared remarks, we will hold 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 Therapeutics core technology, 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 some actions may differ from those anticipated. You are therefore cautioned not to place undue reliance on such forward-looking statements, which speak only as the date hereof. With that, I will now turn the call over to Ulrich.

Thank you, Manuela. As we head into the end of the year, I would like to capture our progress from the last quarter and provide an update on our clinical development plan for varoglutamstat. As many of you know, the Alzheimer's disease landscape continues to be challenged by the regulatory, safety, and efficacy hurdles. At Vivoryon, we are fully committed to make a meaningful difference to all of the people affected by this devastating disease. Our expertise in creating small molecule medications enables our in-depth understanding of pathological pathway as well as to develop the pipeline we have in place today, and we are incredibly proud of the advances we have made as we work hard to improve the life of those who are affected by severe diseases. By modulating the misguided activity of enzymes involved in disease onset and progression with small molecule inhibitors, we are able to disrupt the treatment landscape for indications where the unmet needs remain incredibly high. Our approach to targeting Alzheimer's disease is very different from antibody-based approaches and from those that focus solely on the amyloid plaque removing aspect of the disease, and we are acutely focused and committed to making a difference for all patients affected by this disease. With a specialized approach, we feel that we are at the cutting edge of innovation within the landscape of consistent challenges. As a reminder, varoglutamstat blocks the activity of glutaminyl cyclases, QPCT and QPCTL. The inhibition of QPCT prevents formation of neurotoxic N3pE Abeta, a toxic Abeta variant shown to display a pivotal role in the development and progression of Alzheimer's disease. Importantly, this happens way upstream of other approaches. Moreover, QPCTL fully activates the pro-inflammatory signaling molecule CCL2 by turning it into pE-CCL2. So by blocking QPCTL activity, we are able to reduce neuroinflammation. Both CCL2 and N3pE Abeta are promoters of the downstream tau pathology, meaning that we can also address this pathology via both elements of varoglutamstat mode of action. So varoglutamstat is modulating all the important pathological hallmarks of Alzheimer's disease: Abeta pathology, neuroinflammation, tau pathology, and therefore, can protect synaptic function. To our knowledge, varoglutamstat is the first small molecule and only program in clinical development selectively targeting the de novo production of neurotoxic N3pE-Abeta. The benefit of a small molecule in this disease setting continue to be evident as we observe strong safety results across both of our clinical trials for varoglutamstat. VIVIAD, the Phase IIb trial in Europe and VIVA-MIND, the Phase IIa/b trial in the U.S. We have thoughtfully designed our development program capturing regulatory parameters and specifications as we think about the late-stage advancement of varoglutamstat, while factoring in recent developments within the Alzheimer's disease treatment landscape. As such, today, we are announcing key updates to the development program for varoglutamstat, and we strongly believe that these changes put us on the optimal path for potential approval and ultimately addressing the unmet need that remains for patients with Alzheimer's disease. At the beginning of Q3, we reported data from VIVIAD showing that varoglutamstat is well tolerated at doses with high target inhibition. Importantly, both the total number of SAEs and the discontinuation rates were considerably lower than the respective numbers at the 800 milligram twice daily varoglutamstat dose in our completed Phase IIa SAPHIR study. So by carefully designing VIVIAD based on earlier clinical results, we are able to achieve improved tolerability for varoglutamstat without significantly sacrificing target engagement. The highest dose investigated in VIVIAD, 600 milligrams twice daily or BID, selected as the final dose, it is important to understand how we can best leverage this information to improve VIVA-MIND. Factoring in these highly encouraging safety data as well as the recent data reported from both lecanemab and gantenerumab, including insights from parameters such as readout time points and treatment duration, we have elected to adapt our clinical status. We have carefully crafted a well-defined clinical development strategy, and we are pursuing a newly regulatory path to a potential approval for varoglutamstat with options for surrogate markers, reflecting patient benefit beyond the simple endpoint of plaque-removing potential. This entails a few new factors. We are looking at the combined result of both of our ongoing Phase II studies to offer novel surrogate endpoints. For VIVIAD, we are looking at a composite evaluation of attention and working memory as primary endpoint. In VIVA-MIND, we have selected CDR sum of boxes, a known approvable endpoint as a complementary primary endpoint. Importantly, as we are conducting clinical development in a field that has historically been characterized by a number of setbacks, we have ensured that both VIVIAD and VIVA-MIND studies have been set up as in [indiscernible] studies. What we mean by this is that the design allows for a certain degree of flexibility to adapt to the overall [indiscernible] landscape evolving based on [ insights ] from our own and external data readouts. How did we arrive at these new changes? We evaluated both our own studies and taking key learnings from the results and challenges of our peers to determine the best path forward for varoglutamstat, and we have identified what we believe are 3 critical success factors for an Alzheimer's disease stock. Firstly, patient recruitment and retention in the service. Despite the COVID-19 pandemic, thanks to the careful design of VIVIAD and the close relationships we have built with the study sites, we have had zero COVID-related discontinuation. Overall, the study discontinuation rates are very low, around 6% to date with the study running over 2 years already, which makes us confident that VIVIAD will achieve the necessary [indiscernible]. In addition to the above-mentioned factors, we believe that this is also attributable to the fact that as an oral drug, varoglutamstat requires less time in which participants are hospitalized during the study compared to antibodies and that the study site and personnel were extremely well trained to ensure comfort level and quality standards in managing the specific elements of the study, like, for example, EEG or CSF data collection, which are not standard and therefore need to be established at every site. Consequently, recruitment was comparatively slow in the first 12 months of the VIVIAD study, and we are currently seeing a similar pattern with recruitment into VIVA-MIND being slower than anticipated over the last week. [indiscernible] will be ramped up and training at the study site, in particular, in the context of frequent [indiscernible] and personal fluctuation in clinical study sites across the U.S. As it is our intention to allow for the highest possible degree of flexibility to the VIVA-MIND study, in addition to the primary end point, the design includes data collection for a large number of analytics, composite measurement and secondary end points, which, in turn, makes the study more complex in the initial stages. This poses an extra berm in times where the staffing situation at many sites in the U.S. is [ comfortable ]. Secondly, endpoint selection. Looking at endpoints in Alzheimer studies, the question is always, what does therapeutic success look like in terms of memory, which is why we are evaluating a composite memory endpoint as well as [indiscernible]. The second element of relevance when looking for potential approval endpoint is the question of how the quality of life of patients improves, which is why we have selected a functional end point. That is, to our knowledge, the most sensitive and meaningful enabling us to assess real-life improvements. In addition, by employing EEG, we have added an endpoint, which is not [indiscernible] doctors or personnel, but is an objective assessment of parameters described to correlate with cognitive decline [indiscernible]. We are also adding sophisticated analysis of neuronal networks to contribute to the overall understanding. And finally, balance between safety and efficacy. 600 milligram twice daily has been selected as final dose and [indiscernible] up titration from 50 milligram once daily to 600 milligram twice daily or BID over the course of 12 weeks. The most important learning from VIVA-MIND in its initial stage is to understand that 600 milligram BID can also be safely administered when following a more aggressive up-titration machine, starting at 150 milligram BID and going to 300 milligram BID and up to 600 milligram BID over the course of only 8 weeks. Such a quicker up-titration machine [indiscernible] routine as compared to the slower regime we've been using in the VIVIAD design. Turning now to more specific updates for each trial. For VIVA-MIND, more than half of the 600-milligram BID cohort has been treated with varoglutamstat with no adverse events of special interest observed to date. Based on the encouraging safety data, we have decided to treat all 180 patients in that trial for at least 72 weeks. With this adjustment, we are shifting focus of the study to better prepare for potential transformation into a Phase III study in the event that this would be required for accelerated approval. We have a high degree of confidence to move forward with the 600-milligram BID initial dose, and we look forward to observing longer-term follow-up for all patients up to 72 weeks. This change enables all patients in the Phase II portion of the study to receive longer treatment than the originally planned 24 weeks. And on this basis, we expect to have key data in hand to make even more informed decisions about next steps for the program as well as having a more informed trial by taking into account learning from VIVIAD as our European study progresses through final stages. So to summarize, all 180 patients included in the Phase IIa portion of VIVA-MIND will now be treated for 72 weeks to increase quality and robustness of data and allowing the seamless transfer into potential confirmatory safety study. This prudent adaption is designed to increase the probability of success of the VIVA-MIND study for potential group. Consequently, we are no longer guiding [indiscernible] into a futility analysis as basis for a [indiscernible]. We intend to provide a safety update on the study in the first quarter of 2023. Now regarding VIVIAD. As a reminder, this is a state-of-the-art Phase IIb study conducted in Europe and designed to evaluate the safety, probability and efficacy of varoglutamstat in subjects with mild cognitive impairment and mild Alzheimer's disease. We are very happy to report that we have completed recruitment into the study as planned. VIVIAD is now fully enrolled with a total of 259 patients. We've designed this trial with study protocol flexibility to optimize treatment duration. As Alzheimer's disease is a slow progression disease, longer treatment duration is expected to help data quality and facilitate observation of treatment effect. We are now aiming to allow all randomized patients who have not completed 96 weeks of treatment to have their last visit up to year-end 2023 as opposed to stopping all data collection to the last patient 48 weeks estimated for October 2023. This step will allow us to collect additional data, improve overall data quality and increase the average treatment duration for patients. So this means that over 100 patients will be treated for 96 weeks and over 200 patients will be treated for at least 72 weeks to the mean treatment duration of approximately 82 weeks. All of these are estimates based on the current discontinuation rates, which, as I mentioned, are particularly low at only 6% in VIVIAD. It is important to note that this will be among the longest treatment duration for such a comprehensive study in the Alzheimer's disease field, and we are excited to be at the forefront of this effort. In addition to the final follow-up visits in the second half of 2023, we had previously guided to, we now expect reporting of full data, including additional follow-up data in the first quarter of 2024. I'd like to note that to date, we continue to be incredibly encouraged by the results observed from varoglutamstat thus far as it was well tolerated in our Phase I clinical study, and we've gained important information on those response and target occupancy. And as mentioned before, our first trial for patients with Alzheimer's disease with Phase IIa SAPHIR study met not only the primary objective of obtaining important safety information, but we were also able to show first evidence of the modifying activity of varoglutamstat most importantly with statistically significant changes from baseline in working memory as an important cognitive ability after only 3 months of treatment. Both our VIVA-MIND U.S. and VIVIAD [ Europe] studies are designed to align with the draft FDA guidelines, which supported by the more frequent interactions we can benefit from due to our fast track designation, may provide further regulatory opportunities such as break-through designation and accelerated approval provided both are relevant criteria in the context of our studies and the outcomes are fulfilled. So in summary, our overall data set is intended to support a clear path for approval for varoglutamstat and we strongly believe that the update to its development plan that we've announced today further supports this path. We look forward to providing further updates on our progress, and I would like to thank the patients, their families and caregivers and all supporting staff at our clinical study sites for both VIVIAD and VIVA-MIND and with this enabling advancement of science in this very important field. I would now like to give an overview of our financial results for the 9 months ended September 30, 2022. The company did not generate any revenues in the 9 months ended September 30, 2022, whereas in the first 9 months of 2021, revenues amounted to EUR 10.8 million, deriving from a strategic regional licensing partnership in China. From January to September 2022, our research and development expenses added up to EUR 16.1 million compared to EUR 13.6 million in the first 9 months of 2021. This increase was mainly driven by EUR 1.9 million higher expenses related to our trial VIVIAD. General and administrative expenses totaled to EUR 4.2 million, an increase of EUR 1.0 million compared to the 9 months ended September 30, 2021, mainly resulted from higher expenses for share-based payments for a new share option grant in 2022. Net loss for the period ended September 30, [ 2022 ] amounted to EUR 18.9 million compared to EUR 7.3 million for the same period 2021. The company held EUR 19.8 million in cash and cash equivalents as of September 30, [ 2022 ]. And please note that the proceeds of the price placement entered into on September 30 are not yet included in this cash number. Total equity stands up to EUR 20.1 million on September 30, 2022, compared to EUR 16.6 million as of December 31, 2021. And with that, I would like to thank everyone for joining us today. We've already remained in a strong position as we head into the end of the year, and I would like to reiterate our enthusiasm around the new development changes for varoglutamstat announced today. We have a clear opportunity to address all [indiscernible] Alzheimer's disease by modulating QPCT and QPCTL activity. We are at a critical time in Alzheimer's disease research with multiple wins expected occurring throughout these. Ultimately, our primary mission is to address the continued extreme unmet need for these patients and to meaningfully ameliorate the global Alzheimer's disease crisis. I will once again like to thank our shareholders, many of which have been following our progress for many years now for their continued support and welcome our new shareholders. We look forward to keeping you all updated on our progress, and we will now open the call to take questions. Thank you, Timo.

[Operator Instructions] The first question is from the line of Joseph Hedden with Rx Securities.

First one on VIVIAD, could you just expand a little more, please, on the decision to essentially lengthen the trial. Is that from observations that you've been making in the literature? Is it [indiscernible], is there something intrinsic about the trials and you weren't quite happy with just a little more rationale please would be great.

Yes. Thanks, Joseph, welcome to the call, and thanks for the question. I think first and foremost, I mean we are carefully observing what kind of peer data is appearing in the recent months and what we are particularly referring to is the observation that we see a meaningful separation between the development of placebo outcome parameters or clinical endpoints and those with active drugs separate at a later time point as the consensus expectation was. And this is an observation we made with lecanemab, in particular. And that was one trigger point where we decided to use the flexibility of the study protocol to treat the patients longer as originally planned. As you know, usually, the last patients completing 48 weeks of treatment would have determined the treatment stock of all patients in the trial, and we have decided to alter that and let the patients continue treatment so that they can have their last visit still in the year 2023.

Okay. And if I could have one VIVA-MIND too. So obviously, the design has changed a fair bit there allowing potential to go into Phase III. So what should we expect at the Q1 update? Is there going to be a decision at that point whether you instead of it becoming a Phase IIb going to Phase 3, I noticed that the wording in the press release is Phase III, if required. So is there some kind of regulatory interaction happening soon where you're discussing the potential for an accelerated pathway, I'm not sure quite what the statement, if required, it means at this point.

Yes. And also thank you for that question. I mean first of all, what did we do in VIVA-MIND? So we decided instead of having this [indiscernible] after 24 weeks of treatment based on the first 180 patients which would have led to treatment post essentially, we decided to treat all 180 patients for 72 weeks. So that was the first decision we took. And then as to your question, so what is our anticipation as for regulatory requirements? And you might have followed that there's a discussion also led by lawmakers in the U.S. as to what should be the criteria for an accelerated approval. And obviously, there was some kind of frustration about the fact that some companies have used the accelerated approval and to slow down their confirmatory Phase III trials post approvals. And there might be a situation where there is a requirement to have the season enrollment already achieved in a Phase III trial prior to an accelerated approval. So that might be a situation that may arise. It's not decided yet. But in anticipation, we just thought it's prudent to kind of increase optionality for VIVA-MIND and have a seamless transition into Phase III, again, if the business is [indiscernible]. And as to what you can expect as an update in the first quarter, if we knew that, we have given that. So we just have to be adaptive to the situation. But what we made clear is we will give further guidance in the first quarter as to our further plans with respect to VIVA-MIND.

The next question is from the line of Dominic Rose with Intron.

This is Dominic from Intron Health. I have two. My first question is, in your opinion, is there any read through to Vivoryon from the gantenerumab readout? And that applies to either varoglutamstat or to your antibody? And then question two is can you give us an update on your latest thinking on licensing glutamstat outside of China? And I'm thinking not so much for the U.S. here as well as the rest of world regions.

Yes. Thank you, Dominic, for your questions. As far as gantenerumab is concerned, which clearly was another disappointment in the field however we are not at all discouraged by the outcome of gantenerumab. And I think there's an important difference between gantenerumab and lecanemab. So lecanemab, obviously, is acting more upstream with respect to the aggregation cascade of Abeta. So lecanemab obviously is binding to soluble aggregate of Abeta, whereas gantenerumab is more downstream in this aggregation process and focusing on already established and soluble aggregator of plaque. And in that respect, it's similar to aducanumab. And therefore, it's not necessarily a surprise to us that there was a different outcome in the gantenerumab trial versus lecanemab. So if there's a cross-reading I would say, it's important to act upstream in the process, and we are even more upstream than lecanemab because we are preventing the formation of toxic elements in the Abeta aggregates rather than removing them once they are established.

That's very helpful. And on the licensing?

Yes. I mean, our thinking on licensing is that it's an important part of our strategy because the more downstream we are developing our programs, the less particular value we may be able to add. And this is why partnering is a key priority in our business strategy. However, I think it's important for us to be able to achieve the important value inflection points in both of our trials, and we want to make sure that we are able to do that. And yes, I think in terms of the future of the program, it's going to be very important to have the [ VIVA ] data available. And I think we have tried to point out to-date that we have a study here with very high integrity with very low dropout rate, high compliance of the patients and we are quite sure that the data we will see go to. Does that answer your question, Dominic?

The next question is from the line of Alexander Galitsa with Hauck Aufhäuser.

Yes. Can you hear me?

Yes, we do.

Okay. Good because I wasn't sure I was struggling with my microphone here. So I just wanted to ask around the sort of value capturing possibilities in your key Alzheimer's assets if maybe we'll start with varoglutamstat. Could you broadly talk about kind of your strategy, how you see it around whether you would be looking to partner prior to the marketing authorization being received or would you be looking into doing that right after. That would be the first one and then I'll follow.

Yes. I mean this is kind of a similar answer to the last question. Again, I mean, partnering is an incredibly important element in our business balance sheet. And yes, of course, we want to be positioned as well as possible with our trials, with our data. But first and foremost, it's important to us to make sure that we are able to achieve the next -- or the potential value inflection points in our clinical trials. And as the time point of when we are able or when we want to enter into a partnership, we're kind of opportunistic. And of course, it also depends on the match of the economic potential of what we might be able to offer to the market.

And then if I continue with the N3pE antibody. So what one can expect here? Would you -- are you looking to partner it already now or are you still planning to do some work internally before you will consider partnership? And maybe also in connection to that, I think you mentioned earlier that you will be running another combination trial preclinically. So if you could update us on that, whether they are undergoing and when can one expect any kind of readouts or results from those?

Yes. So first of all, we are working on our antibody, and we are expanding the base of data, which we are able to show with respect to this antibody. In terms of combination, which you were mentioning, we are much more focusing on varoglutamstat here because we believe that this is a very attractive additional opportunity to position this drug on top of a monotherapeutic setting, which is, of course, what we have in mind in the current development strategy. But we believe, given the safety profile and the combination data that's already available that we have an additional attractive option or opportunity to position varoglutamstat also in a combination setting to the antibody. And for the antibody and the partnering strategy, similar things apply, as I mentioned before. So we are exposing ourselves here. We are opportunistic and at the same time, are adding to the profile of this antibody.

And then maybe briefly on the oncology opportunity. So right now, you're basically in a situation where your focus is on Alzheimer's. And so the organization does not necessarily have the bandwidth or funds to further develop the immuno-oncology franchise. So naturally, one would expect you to partner license the IP. And I'm wondering sort of from today's standpoint, what is sort of the major roadblock, so to speak? Is there a lack of interest from the big pharma? Is that that the IP is too early in the stage or there is anything else?

Okay. Thank you, Alex, for this question. Understood. I mean, first and foremost, when you've mentioned that we only have a limited operational and financial bandwidth. And currently, we are laser-focused on progressing our equipment staff to clinical development as we [ plan ] today. Now having said that, what we have to acknowledge in the field, especially of CD47/SIRP-alpha signaling is that most of our peers have advanced clinical data. Of course, they are based on antibody approaches, but this is clinical data. And it is obviously challenging to compare preclinical or research data with advanced clinical data. So in terms of strategy, we are looking into is possibilities through partnerships or other measures to make sure we can progress this concept into clinical development and kind of backing our claims, which we have been making on a preclinical basis in clinical settings. And I think that's the key to success. And we are absolutely excited about the opportunity we have enhanced here, and we are continuing to make sure that we exploit the full potential of these assets.

And the last for me is regarding KKR sort of engagement so far. Have you noticed there sort of activist angles and they have made the investment or is it still too early to tell anything?

Yes. I mean, so the activist angle sounds a little bit kind of negative to us. But what we can confirm is that they have broad network work, and they have the preparedness to make this network available to us. And we are very excited about the collaboration with KKR. Of course, it's early days, but we already had very interesting interactions, which we will continue over the next, yes, couple of weeks, and we are really excited about this new partnership.

That's the way I meant it really leveraging their network potentially relevant not necessarily in a negative sense.

[Operator Instructions] The next question is from the line of Christopher Redhead with goetzpartners.

Just in terms of the -- you're extending the treatment time, right, for the -- in the trial. And because you -- the data suggests the other data suggests from -- that was from other -- the antibody trials, right? There's more -- a greater divergence between drug and between -- yes, between control and drug in those trials. How -- just can you just sort of remind us about how big that -- how much that is? What is the kind of difference in magnitude of the divergence because clearly, that's going to be pretty significant? That could give you accelerated approval couldn't it? Because if you get a much larger effect at that time point, you could get accelerated [indiscernible] become a much more attractive licensing target. Could you just sort of kind of give us a little bit more color on that?

Yes. I mean what we can't give you is a very precise benchmark. But what we have seen is obviously that the treatment duration is a critical success in Alzheimer's disease. And you obviously know that there is also kind of discussion around speed of progression between different genetic settings, for example. And we really want to make sure that with the treatment duration in this very important trial for us, we kind of exhaust the flexibility which we have within the given study protocol. And this means, again, that we are expecting to have an average treatment duration in this trial of 82 weeks, which is substantially longer than most of the standards which are focusing on 72-week data.

The next question is from the line of Gilbert Gerber with Belsize Asset Management.

I was just wondering, in fact, Joseph already touched on that question, but I'd like to have a bit more color on that. It's about the transition to Phase III. In terms of what would it look like in the first place? And have you been, let's say, in interaction with the FDA about what these conditions would be? And would it be really realistic to, let's say, make a decision on that before you have the European trial data. So that's -- this whole complex I'd like to have still a bit more explanations.

Yes, Gilbert, welcome on the call, and thanks for this question. I mean again, as I stated before, what we have to deal with currently is the draft guideline situation. So we cannot a 100% be sure what will be the situation when we have the data available. And what the amendment or what the alteration of the trial design of VIVA-MIND is meant to is to, first of all, avoiding that we have treatment process in a slowly recruiting trial, which would have been a risk if you would have to test all 180 patients at 24 weeks of treatment and secondly, to increase optionality. So in that, we treat seamlessly all those 180 patients for 72 weeks that can mean different things, that can mean that we would be able to add additional patients while we treat those 180. That can mean that we adjust our statistical modeling once we have the readout of VIVA available. And that could mean that we extend the trial beyond the treatment of 24 weeks of the first 180 patients. So all those options are possible, maybe even additional ones. But the goal really is to create optionality and especially to be able to have a more seamless transition from this Phase II trial -- in a Phase III trial, if regulatory environment is requiring that.

Okay. And maybe the second one is concerning the antibody, as you probably would have guessed. It is as much a statement as it is a question. Eli Lilly has leapfrogged their follow-up antibody to donanemab. They must still have problems. Remember, [indiscernible] from a Phase I to a Phase III. So yes, from an investment point of view, it makes sense to focus everything on the small molecule. But I was just wanted to -- for the record, make sure that all options are evaluated in order to bring that program, which, in my opinion, is the best-in-class forward as soon as possible. That's about it.

Yes. Thank you, Gilbert, really acknowledged. And we are also happy with the kind of focus that Lilly is putting on N3pE based approaches, which is also kind of endorsement of our approaches, both approaches the small molecule and the antibody one, but really acknowledge your statement, which we are perfectly sharing with you. I think it's a great asset and deserves to be developed.

[Operator Instructions] The next question is from the line of [indiscernible] with [indiscernible] Asset Management.

You haven't said anything on the China development in your note this morning on Simcere. Could you update us on the preparation for Phase I and maybe any likelihood of a '23 payment -- milestone payment?

I pass on this question if you allow to Michael Schaeffer.

Yes, we are certainly continuously in discussion with Simcere how to design and pursue the clinical development in China. So that's an ongoing process. You might be aware of the fact that we are in a phase where we have changed with the plans in terms of -- we put this study in terms of the Phase II part, do it in sort of a parallel extra cohort with the European trial, which we changed towards the U.S. trial, which just has the kind of approval endpoint with the [indiscernible] boxes. So that may certainly much more sense. And so -- and since we are looking here into a little bit of flexibility, how the U.S. trial is designed in the future, there's certainly just room for -- or need for discussions and for being flexible. We cannot, at the moment, guide to any time point where a Simcere because it's a complete decision of Simcere to kind of start the clinical Phase I, if you will, which would be a prerequisite for these 2, obviously, when this will happen. But again, we are -- of course, all sites are very interested. I mean, Simcere took this license diverse for a reason also. So we are all very interested to move this forward as soon and also as diligent as required.

And do I understand you're right that you're still in a planning phase and you haven't identified any patients yet?

Well, actually, for the Phase I part, the patients would be kind of available, if you will, because Simcere has kind of established Phase I unit. So that would not be like a bottleneck or something like that.

Okay. And payments then for '23 up very unlikely then from what I hear you're saying?

I'm not sure what I got you right. I mean they have to do the Phase I to have the optionality to whatever to do in a Phase II. I think they are appreciating that, and we expect that they are committed to starting Phase I. I think there's another aspect which we should mention, and this is due to the COVID policy in China. I think that's also an element which has a certain impact as to their ability to move quickly with clinical trials in China.

Yes. Just repeating -- likelihood of any milestone payments for 2023 is rather unlikely, correct?

If they proceed according to plan, I think it's likely.

The next question is from the line of Alexander Galitsa with Hauck Aufhäuser.

Just one follow-up. Could you just explain why have you decided to go ahead with the adaptive dose finding part instead of dosing all patients with 600 milligrams given that you have kind of cleared the safety hurdle with your interim safety readout.

Alex, to be clear here and I think we communicated that today. Our assumption is that we feel we have a high safety potential at a dose level of 600 milligrams. And this is underlined by the fact that we have already enrolled 40% of the 600 milligram cohort in VIVA-MIND, excuse me. And so there's a lot of evidence that lets us believe that this is going to be the dose for all 180 patients, which we are treating for the 72 weeks.

There are no further questions, and I hand back to Ulrich for closing comments.

Yes. Thank you very much, Timo, and thanks, everybody, for joining our call today. Yes, I'd like to, again, thank you. And yes, please stay tuned, and we look forward to talk to you at the next occasion. Thanks very much. Bye-bye.

Ladies and gentlemen, the conference has now concluded, and you may disconnect your telephone. Thank you for joining, and have a pleasant day. Goodbye.