Nykode Therapeutics As

Greetings, and welcome to the NICO Therapeutics Q2 2024 Financial Results Presentation. At this time, all participants are in listen-only mode. There'll be a question and answer session following the formal presentation. You may ask a question anytime by typing it into the Ask a Question feature on your screen. As a reminder, this conference is being recorded. It's now my pleasure to introduce your host, CEO Michael Ensig. Please go ahead, sir.

Thank you very much, Kevin. And also from our side, a very warm welcome to all participants at this webcast to go through the second quarter of NYCODE's results. With me today, I'm pleased to have Arne Frederiksen, Chief Scientific Officer and Head of Business Development, Harald Govind, our Chief Financial Officer, and Claus Edwardsen, Head of Research and Development. We assume you're all familiar with our forward-looking statement, so on that note, we'll just quickly skip forward. So, test quarter has been another eventful quarter, and in addition to that, we have this morning also announced a strategic repositioning, which will take you further through I'm going to give you a brief rundown of the key highlights and then I'm going to hand over the words to Klaus to take us into the rational and thinking behind our repositioning. Then I'm going to hand over the word to our leader to take you through some of the exciting updates we have from our technology platform. And finally, Ahal will take us through the financial highlights. This morning, we announced a strategic repositioning of our BB1016 development plan. to refocus the program on two key indications, locally advanced cervical cancer and recurrent metastatic head and neck cancer. And this decision comes on the back of very positive feedback from our key opinion leaders as well as potential future partners regarding these two indications. These two indications have been chosen by us because they do represent areas where we see a large unmet medical need as well as a significant commercial potential. We have consequently decided to discontinue the CO4 trial and that decision comes on the back of changes in the dynamics related to the standard of care which was impacting the timing of the trial which in the end put some challenges to the whole strategic rationale of our faster market strategy for VP1016 in the recurrent metastatic circuit cancer and we therefore decided to allocate the funding to the locally advanced circuit cancer at the metastatic head and neck cancer because we think they represent more valuable areas for the company. We have also To further emphasize the positive sentiment around the locally advanced cervical cancer area announced during the second quarter, the agreement with MSD to supply Keytruda for our CO5 trial, which will be our first trial into the locally advanced cervical cancer treatment. And we'll have Klaus tell us more about the background and the rationale and our enthusiasm for that trial when I hand over the word to him. Further along the decisions to reevaluate our allocation of funding, we have decided also to discontinue further activities on the NIC11 preclinical program, and that also comes as a consequence of our focus to really concentrate our both capital and human resources within the oncology segment on our partners and programs and our clinical assets. We had a key patent issued in the U.S. around our individualized neoantigen-based vaccines. Anita will tell us more about that patent when we hand over the word to her. We presented very exciting data from our ABC-targeted neoantigen vaccines in the mRNA format, which shows again its superiority over antigen-alone vaccines formulated by mRNA. We've presented advancements in the inverse vaccine platform, which is our use of the technology within the autoimmune disease area, which highlights the versatility and effectiveness of NYFO's ABC-Targon technology in this area. And we have revealed plans to form a new subsidiary focused on advancing our immune tolerance platform further. Again, a quick look at the pipeline, which have been modified to reflect today's refocusing. So again, you want to emphasize or bring the attention to BB1016, our lead assets. Again, I want to emphasize we continue to have a very high level of conviction in BB1016 to benefit patients. across a range of diseases. We're now focusing on head and neck and locally advanced. And we'll, as I said before, update you a little bit more on the programs as they are running when we hand over the word to Klaus. Also seeing exciting development on our other programs, not least the Regeneron programs that are still moving forward, as well as our partnership with Genentech. With those words, I'll hand over to you, Klaus, to take us through the strategic repositioning of BB 1016.

Thank you, Michael. Klaus here. Good afternoon. Good morning to everyone. Obviously, the IMD update today will focus primarily on the announcement that was made this morning to discontinue the BB CO4 trial. Let me just state upfront that this decision is not based on any data that is indicating that we should lose faith in VP1016, nor any safety data. It is a strategic decision that is purely made for feasibility reasons. And let me try to give you a bit of context for what those feasibility situation is. We have every confidence that we would have been capable of recruiting this trial to completion, but we have to accept that we will be faced with significant delays and therefore have made the strategic decision that those delays are not acceptable for a strategy that was set out as the fastest to market authorization possibility. And therefore, we decided to stop at this stage and reallocate resources, as Michael mentioned, to the locally advanced cervical cancer as well as the recurrent metastatic head and neck cancer. But let me just stay honest to the slide and say that what we have been faced with that has been taking us with a bit of surprise is that the recruitment numbers of this stage are not where they need to be. And that is primarily based on a reason that we are seeing that the consequences of a full approval of TIFTAC, obviously a compound that we were fully aware was present, has not changed the number of prescriptions necessarily filled for TIFTAC, but changed the dynamic of the patient flow. Understood in that fashion that patients with recurrent metastatic cervical cancers is very often entering into the healthcare system in community hospitals and then used to be referred to tertiary cancer centers that are obviously GOG centers and different centers where our partners would see the patients. What seems to have happened now with an element of misjudgment, obviously, from our side, is that that referral is not happening to the degree that we would have expected it to happen. And that's obviously a dynamic of patient flow that NICODE and, for that matter, GOG would have difficulty in changing. And therefore, we came up with the strategic reposition of the program because the fast of the fastest-to-market strategy has somewhat disappeared. If I can have the next slide. I just want to remind everyone that we have always been guiding the market to say that obviously we build a strategy with a fast-to-market strategy. That's the CO4 strategy that I just described. But very intimately linked into that strategy was also to capture a patient population with an equally high on the locally advanced cervical cancer. which is a patient population that is larger than the recurrent metastatic. And if we really look at the data that we have available from the CO2 trial, that we have shared interim data with you and also guided you that when the final results from that trial was read out, that we closely mirrored the interim data but decided not to give you any numbers from the actual trial. I will, although for this call, allude to why the CO2 results were not only important for CO4, but actually more important in reality for the strategy in locally advanced. If you look at the very simple data set, or maybe not that simple because it is a spider plot or a spaghetti plot, if you like. It is, in essence, showing in color blue patients that did not have what's called an objective response, meaning they would have had a tumor reduction of at least 25%. On the other side of the cartoon, it's shown in red, patients that actually did have an objective response in the CO2 trial, meaning that they would have had a reduction of their original tumor size of more than 25%. What you also would see on this slide is that obviously the reds are having a much deeper fall down of the curve. That's because of the response on the tumor. On the blue, you would not see as deep reduction of the tumor, but you would, in essence, for a majority of patients, see a flat curve, meaning that adding the vaccine to standard of care in that experiment led to a maintaining of to feel whether that clinical effect was a response or a stabilization. If you think about locally advanced disease in an adjuvant setting, There you, in essence, treat patients with a definitive treatment, and then you have preselected patients for effects, and then you vaccinate them, if I can use that terminology. And therefore, the CO2 data very, very nicely support that we would go into the CO5 trial with an expectation that the vaccine will add a significant more effect than we would have obtained by standard of care. Next slide, please. So as Michael alluded to and I also alluded to, we will stop CO4 with the aim of focusing on primarily locally advanced cervical cancer. We have already communicated to the market that this is not something that we are in the early planning stages of. We have announced that we did sign a supply agreement with our clinical partner, Merck MSD, and we are imminently ready to release the final design of that locally advanced C05 trial. and would obviously advance that through the fastest possible degree based on the decision of not continuing CO4. And by that, I hand it over to Agneta.

Thank you, Klaus. Then we move forward to the DB10EO program and the update that happened in the last update. A reminder here briefly, Vita Tania is our pre-individualized cancer vaccine. This is where we define one vaccine per patient by using first sequencing or biopsy tissue, define the vaccine to match each individual patient, manufacturing, give it back to the patient. This program, as you are aware of, is exclusively outlicensed to Genentech. If you go to the next slide. very important factor of partnership deals as the one we have with Genentech is the basis of our patent protection for the products and we are very happy to see that we could obtain a grant of this patent for VB10 Neo also now in the US. We mention this particularly because US is then the biggest market for these kind of treatments, and obviously also the country where our partner Genentech is situated. This is also a patent that is not necessarily straightforward. NYCO is one of the pioneers in this field, and to get the grant for a product that is also based on a process of how to design and manufacture these vaccines for each patient, It's a challenge and it's then also very good to see that we have now obtained a grant in these important countries. This gives us also an exploration for lead pattern will last until January 2037. So important for all also the terms in the deal with our partner Genentech. I think we can move forward to an update on the mRNA oncology vaccine. As you know, Michael has so far focused its clinical programs based on the plasmid DNA format. We are a technology company which is based on using a targeted delivery to antigen presenting cells, which in principle is broader than the use of the plasmid DNA format for constructing and manufacturing and delivering these kinds of vaccines. So we have recently then shown and demonstrated before that we can also make these APC targeted vaccines that are proprietary to myCODE as mRNA, and we've also seen that we can improve the number of immunogenic antigens versus the standard antigen alone approaches, which is what you normally see with the mRNA vaccines that you see from other competitors in the field. The new data now from second quarter, which I will go into in a bit more detail in the subsequent slides. is further substantiating this improved immunogenicity. And now across a range of different doses, we still see the superiority and also different time points. We can also show that the bias of the NICOS-APC targeted technology versus antigen alone is focusing on a bias to CD8 keto responses. And we now also can see that this translates into superior tumor control. So very important data to substantiate the opportunity for NICODE also to be a strong competitor to other mRNA antigen alone approaches. If you go to the next slide, this is one of the datasets that were presented in Q2 where we can see here At the bottom, you can see across different dose levels. So we see an enhanced response, actually a response that is significant, even after single vaccination and low doses. And you can see that increasing the doses, we continue to see a strong benefit of the strength of the T cell response. This is what you see on the y-axis here. across all doses and you never see these two curves cross, meaning we maintain the benefit across all doses. That's also true for the panel to the right where we have been vaccinated twice and you can see that we can see a very strong efficacy increase with the vaccine body versus the antigen alone. particularly with very low doses, so relevant for the clinic moving forward. Let me go to the next slide. We have shown before that we see an increased breadth, meaning that there are, for instance, these individualized cancer vaccine settings is where we predict and include normally up to, for instance, 20 new epitopes into one vaccine. We always wish to have as many of these neoepitopes actually translating into an antigen-specific immune response in the patients. And here we show that we can up to double the number of neoepitopes that are immunogenic compared to the antigen alone vaccines. Again, we see the antigen alone vaccine is not catching up to the same level of breath with high doses. And to the right, you can see this skewing. So you see the immune response is highly focused on CD8 T cell responses versus the CD4 helper T cell responses. But obviously, we also find it important that we do see some CD4 responses. The number of colors on the column indicates the same breadth that you see on the other slide. So you can see more colors, meaning that there are more targets for the CD8 T cells to recognize on the tumor cells. And then finally, in the next slide, we can see that this enhanced immune responses that we've looked into in detail actually translates into superior tumor control, where we see a statistically significant difference between the ability of Nyquil's vaccine with exactly the same set of antigens and translates into the tumor efficacy while we don't see a statistically significant protection here with the antigen alone vaccine. So this is always a question whether we are moving into being an mRNA vaccine company. For us, this is about having a basis and knowing that our technology works across different formats and formulations. It is super helpful for us to show the direct efficacy of the antigen presenting cell technology, the targeting to antigen presenting cells here also across different formats and formulations. And importantly, it provides the basis for a much broader set of potential partner discussions.

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Yeah, and sorry for that. We lost connection here from the office, and now we're back. I think you heard through the MRNA session, so let's move on to the autoimmunity platform update. I think you can go to the next slide. So just a short reminder of our immune tolerance platform, our inverse vaccines, is building on the years of experience with the APC targeted technology, but with then an important twist. So we changed certain parts of the technology to make sure that The antigens in this case is directed to different subsets of antigen-presenting cells in order to then control that the immune response goes in the direction of inducing tolerance against the specific antigens included in the vaccine and not as stimulating immune response that we focused on in this call up until now. I think we can go to the next slide. And NICODE has also in Q2 been at a conference and presented some updated data which continue to highlight the benefit of using the APC-targeted technology in these preclinical models for autoimmune diseases. We have now tested here two different targeting units. So as you know, we have the to use different targeting units, which will make sure that the antigens are directed to different receptors on different subsets of antigen-presenting cells. And by that, we can see the end result being different immune responses against the antigen included. So here, using two different targeting units that we believe induce tolerance. And we see that it is possible to do this. And then we can go to the next slide. This is where we see the two different targeting units. And we can also see, actually I have to go back. Now one, I think here is actually the focus on how this separates from the antigen alone vaccine. So we can see here in a pretty, late stage disease where the mice have actually developed signs of disease with an EAE score here of one. We can see that antigen alone here in black is not able to show any therapeutic efficacy, but we do see therapeutic efficacy with the high dose of our vaccine. So it's showing we can induce this effect in mice that are even one step thicker than what we've shown before. And in the next slide, then, we have then repeated this experiment with two vaccine bodies that have different targeting units, as I alluded to before, and see a statistically significant durable, long-lasting effects in a therapeutic setting. So if you go to the next slide, the new data, I think, highlight the versatility and effectiveness of our ATC-targeted technology, which we believe has a broad applicability across the field of human tolerance. This is a preclinical model. The mechanisms or actions we believe can be incorporated against both autoimmune diseases, potentially allergy, organ transplant rejections, et cetera, in the future. So these are models that we believe is very important for the future of a broad set of potential product development. announced in this quarter that we have taken a step and establishing a subsidiary that is focusing on immune tolerance in order to put our efforts into advancing this, showing that we believe that this subset of our technology has a lot of value by itself and get enough attention and visibility out there for using to continue to benefit patients as well as providing shareholder value. I think we can go to the next setting. I will then hand over to you, Harald.

Thank you, Agneta. Looking at the income statement, we reported total revenue close to $600,000 in the second quarter, of which $540,000 relates to R&D activities delivered under agreements with GMN Tech and Regeneral. Employee benefit expenses were $5.7 million in the second quarter, up from $5.1 million in the previous quarter, for the same period in 2023, reflecting the growth in the organization. Other operating expenses reduced over 6 million, down from 11.4 million in the same period in 2003, mainly reflecting reduced costs following finalization of enrollment under the NO2 trial. Financed income was 2.9 million in the quarter, which mainly relates to interest income, while financed costs of 0.6 million mainly relate to unrealized currency losses on the wheeling crown or exposure. So overall, we recorded a net loss of 7.4 million for the Then moving on to the balance sheet, we had a strong cash position of 136.5 million in the quarter ends. As previously communicated, we received a decision from the Norwegian tax authorities in the fourth quarter of 2023, where they reiterated a position that upfront payments received under a license agreement entered into in 2020 should be recognized as taxable income in full in 2020, rather than the usual taxable gain-loss account. The decision generated a payable of approximately 30 million in the fourth quarter of 2023. NYCOD is confident that the use of taxable gain loss account is the correct treatment of the upfront payment, which is also being confirmed by third-party tax experts. NYCOD has appealed the decision, and the payment has been booked as a receivable by the outcome of the appeal. Next slide, please. Then moving on to equity and liabilities, we have total equity of 152 million, which represents a strong X-D ratio of 85%. And with that, I will give the word back to Michael.

Thank you very much, Hans. And just to finish off with the outlook for a coming period, as I said in the beginning, it has been a hectic period. And I think 2024 has been a very important year for VB1016. We reported the very encouraging final conclusion from the CO2 trial. which, as Klaus told you earlier today, closely mirrors the conclusions we have seen from the interim, which again points to a very strong clinical effect, very strong immune responses, which translates to durable responses We are, despite the decision to discontinue CO4, very committed to advancing VB1016 as our lead asset into the areas of locally advanced cervical cancer as well as head and neck. Within the latter, we have already started the CO3 trial and we expect to be able to select the recommended phase 2 dose in the PO1 positive patients from first line recurrent metastatic head and neck towards the end of the year, and this, of course, will be an important data point information for us as we design the next phase or next part of the head and neck program. In the autoimmune disease field, we have already this year been reporting quite a number of very encouraging data that speaks to the concepts and feasibility, and we continue to push forward, generating more information and data around that technology. and look forward to keep you all posted as we progress forward towards selecting both indication and the plan and the path forward. Also, in the mRNA space we continue to see exciting data and are still investing resources in exploring what we can do in that area And we'll, of course, also take this into context for a partner strategy. And we also here look forward to be updating you with further news and data towards the second part of this year. So, exciting times ahead of us. Despite the news around the discontinuation of CO4 today, I hope you appreciate our own conviction and enthusiasm for BB1016. We believe we have a unique product here that has the potential to provide benefits for patients across a range of indications and are as committed as ever on taking this asset forward in the very attractive areas of locally advanced cervical cancer, as well as head and neck, not least based on the positive feedback and input we've had from the external community, both the medical environment and potential future partners. And with those words, I think we are at the end of the formal presentation and can open up for questions. Kevin.

Thank you. We're now conducting a question and answer session. As a reminder, if you'd like to be placed into question queue, please type your question into the Q&A pod located on your screen. The ask a question feature. Once again, to ask a question today, please type into the Ask a Question feature on your screen. One moment, please, while we poll for questions. Our first questions today are coming from Geyer Holm from DMB. In light of the discontinuation of the C4 trial, has your partnership strategy for the VB 1016 asset changed in any way? More specifically, is the company more willing to enter a commercial partnership earlier than before? Is it likely that a partnership can materialize before the CO5 trial initiation?

Thank you very much for that question, Gaia. And just to confirm, and to what extent it's a change, I'm not sure, but we do consider partnership a very important strategic element of our VB 1016 program and are definitely exploiting every opportunity of getting a partner on board, both because we think a partner will contribute with competencies, but also more specifically to offload the development cost. So, yes, we are looking for a strategic partner for VP1016, and it is, at least I can say, not unlikely, and we can define likely, that a partnership could materialize before a CO5 trial will be initiated, but I'm not going to speculate to the likelihood of that happening. I think we'll take the next question.

A follow-up from Geyer is going to be, regarding the Genentech partnership, following the reorganization, You say that you have not received any indications of the partnership being affected. That's a quote. But have you received any reassurance or confirmation that the partnership is unaffected and still prioritized? Could you make any more comment to reassure investors that are concerned following the news?

Yes, again, also thanks here. And I'm always a little bit mindful speaking on behalf of other companies. Still, for those of you who have not followed the news, which are relevant for an iCode here, I'll just remind everybody that it was announced that Aaron Millman will be leaving Genentech and there will be some reorganization in Genentech. I fully appreciate that has caused some confusion concern, especially in the capital market. So let me see if I can put that to rest. We did receive upfront notice that our amendment was leaving Genentech. We were also informed that this was happening as part of a reorganization. What we have further been informed by our partners at Genentech is that the reorganization does not reflect a strategic change from Genentech when it comes to on-call immunotherapy. They remain committed to the area and they remain committed to cancer vaccines and what we have been told relating to our own program is that it is business as usual. And I think this is as much as you can expect a partner to communicate in this kind of situations. We sat on a personal level to see Ira Melman leave. Ira has been a very, very good partner for us for all the years. But at this time point, a partnership with Genentech of this nature is much broader than hinged on one person. So we look forward to continue the very fruitful collaboration we've had with Genentech with a range of people, including senior executives that we have built up over the last couple of years. From our perspective, we do not see this in any way changing the collaboration or the conviction from Genentech. And the next question.

Sure. A follow-up from Geir from DMB is going to be regarding the Regeneron partnership. Could you please comment on the status and progress of this partnership?

Klaus, I don't know if you want to add more, because again, we are not in control, but I think from our perspective, we can say... Thank you for the question, Guy.

Again, I mean, I can say that from the NICODE perspective and what NICODE is and has been supposed to deliver into that partnership is all taken care of. And I have every indication that Regeneron is moving the programs forward with the speeds that they have also indicated to us. But on the exact status on the programs, I cannot comment. That is a Regeneron element. What I can say is that the deliverables agreed in contract and in partnership discussions from my code to Regeneron has been delivered fully at that time.

So we remain very happy with the partnership.

Thank you. Final follow-up is going to be from Gaia. Would you consider downsizing the organization to preserve cash and extend runway?

I appreciate the question, Gaia, and I hope you will also appreciate that for us this is a very new decision that we are communicating fresh out of the press. So we are still assessing what should be the consequences of this decision to discontinue zero form. And we'll, of course, communicate to the organization first and foremost if anything should materialize on that. So I am not in a position to comment on that further at this call here.

Thank you.

Our next question today is coming from Lucy Codrington from Jefferies. Given the CO4 interim readout mid-2025E had been flagged as a potential trigger for partnership discussions, what could be the next key clinical readout for VB10.16 since my understanding is that the efficacy data for CO5 are unlikely before 2026?

Thank you, Lucy, for the question. I will not at this call comment on when the locally advanced cervical cancer data will be available. As I indicated under my presentation, we will have the final design done. right after the ESMO meeting. There is some important elements that we do need to have released at the ESMO meeting which is in mid-September in Barcelona. What I can say is obviously that we are fully aware that we will take into account when we do that final design of the trial that we would have a meaningful interim analysis as fast as we possibly can in that trial concept without jeopardizing the final read from the trial so that we can guide that we are where we think we need to be with regard to a positive outcome in locally advanced cervical cancer. Next clinical readout will be near end of this year or slightly in the beginning of the new when we read out the dose finding and final dose recommendation in the head and neck cancer trial CO3.

And a follow-up from Lucy is could the CO5 trial design include a potential interim look to de-risk the trial as was planned for the CO4?

I didn't have a magical bullet. I think I answered that question before. It will have an interim analysis, but I cannot comment on the detail at this meeting. As I alluded to, we are in the final stages of settling the design, but we'll obviously guide on that as soon as we communicate the final design together with Merck.

And a follow-up from Lucy from Jefferies is, What is the status of the VB10 NEO patent in Europe?

Yeah, so the update this quarter was that we received a grant in the U.S., and you can also see in the slides that this has received approval in Europe. A few other countries, including Russia, India, and Australia, as by now, we have found in Europe, so we are then going through the office actions and will inform you once it will be granted.

And a further follow-up. And a further follow-up. Lucy Codrington from Jefferies. Has the experience in cervical cancer changed your development plans for HNN cancer? For example, whether to also prioritize locally advanced over recurrent metastatic?

Sorry, it's the question whether the change in cervical cancer has changed our strategy in head and neck cancer. No, I mean the change in strategy in cervical cancer is, as I said, purely driven by a feasibility aspect that was not expected up front. And let me be very clear that obviously we're fully aware of TIFDAC. As I also tried to say, patients and the uptake of TIFDAC, I'm not having any evidence that that has changed. What has changed and was not really foreseen based on all of the available feasibility data we had and our partner, GOD, that is recruiting on our behalf had, was not indicating that patient dynamic and patient flow should have changed, meaning that the patients are not referred to the centers that we are engaged with, with GOD. They are staying in community practice and being treated with TIFDAC. That dynamic is maybe not unprecedented, but something that was not foreseeable, obviously became foreseeable as soon as we opened sites that were able to have those patients. The patients are simply not referred into the center that we have the trial CO4 ongoing with. So we are not having any other driver for the strategic change. We are fully committed, fully believing in EB1016. We are fully engaged in making sure that we make this medicine available, potentially, of course, I have to say, because it will have to go through a trial and approval process. Our strategy in cervical cancer will change a bit. I have talked enough about that. Our head and neck cancer strategy is not going to change, but obviously we have to do this in the right order. We will, as also communicated this morning, advance our effort in recurrent metastatic head and neck cancer, and as we have guided on earlier, we will at the right time also advance into locally advanced head and neck cancer, but that's not in the plan immediately.

I can just add to that answer from Klaus. We should not forget that the CO2 data has been performed and the CO2 trial was performed in recurrent metastatic circle cancer patients, second line and beyond. And we do see signs of clinical efficacy and also the safety profile there. So the change as close alludes to Moving from the second line to locally advanced in cervical cancer does not reflect that we believe that we will not be able to provide meaningful clinical efficacy also in referred metastatic settings. We remain confident that we have a broader potential.

Thank you. Our next few questions today are coming from Sebastian Vanderschoot from Kempen. The first two are going to focus on the dose escalation data for 1LRM HNSCC. Could you provide some insight into what the expected data set for the dose escalation part will exactly contain around YE24? Interested whether you will also be able to share efficacy data at that time point?

Obviously, dose escalation is, in essence, potentially three plus, three patients at each of the dose levels tested out. So it is primary to establish whether any of the doses that we are testing, three, six, and nine milligrams, would be safe to give. But obviously, you will have... what responses the patient eventually may obtain or not obtain that I cannot speculate on now because I do not know the data. But there will not be data in the sense that you can say anything meaningful. It will be on a smaller patient number, but it will obviously be an important guidance internally for which those you eventually would like to move forward.

And again, referring to the dose escalation data for 1LRM HNSCC, how do the recent results from other vaccine companies in 1LRM HNSCC, I believe it's called, at ASCO, change your thinking about how to strategically position the program in 1L HNSCC?

It's not changing our speculations. Let me qualify that. I mean, first and foremost, any elements that indicate that cancer vaccination is the right approach is the validation of what we're doing. We have confidence in our vaccine. And I think one of the elements that needs to be fully understood in head and neck cancer is that you have two options. You either position your compound in the very high PD-L1 There you can do monotherapy setting with pembrolizumab or another checkpoint inhibitor and add your vaccine to that design. Or you can try to take more into account lesser PD-L1 expression levels and combine that with chemotherapy. I am not to comment on development programs for other companies, but I think that there could be a distinction in direct comparison with the company that questioned here whether the PD-L1 expression cutoff level would be the right cutoff level. So we are not hesitating in believing that we can position our compound in the head and neck cancer space irrespectively of the competitive field.

And our next question is a follow-up from Sebastian. Regarding the collaboration with Genentech on VB10.neo, I understand that you're restricted in communication, but would you be great to get some color on how the program has been progressing clinically? Also, do you have insight into the data that has been generated in the clinical trial, or what is the extent of your knowledge on the clinical trial results? And also, although there is no sign of discontinuation of the Genentech partnership, We wonder whether you would share the phase one data generated if it were to be returned?

Let me not speculate about any discontinuation because that is not in scope. We have already, as Michael indicated, no indication that anything is changing except Ironman is leaving, which we regret. But it is business as usual. We have an exclusive partnership with Genentech on personalized DNA-based vaccine, and it continues. So I will not speculate about any situation after this continuation, because that's not what we are discussing. I can say, and that is known, that recruitment in the NO2 NEO program with Genentech has completed. I am not aware of the data because the analysis is ongoing, and it is Genentech's sole discretion on when that data set will be released. I cannot get it any closer, and that's not to sound as a broken record, but it is the way the partnership is structured. This is the ownership of Genentech. But the progress is as expected, and as I said, recruitment finalized.

We have another follow-up from Sebastian van der Schut from Kempen. Can you provide some insight into how easy it is to recruit one LRM HNSCC patients relative to two LRM cervical patients? And do you expect this to change given the number of agents that are expected to enter larger Phase III studies within the near term?

I mean, yes, there is competition on patients for any trial concept. I would just address it in the way that I don't think you in general terms can make a cross-indication comparison. It is very individual. Let me see if the background for the question is that we have not landed where we would like to land on CO4, that we have been clearly and transparent communicating to you. We have also been giving you the reason for it. That is a very unprecedented reason with a compound that has admittedly been around for two years on an accelerated approval. and obtained in April a full approval. The patient dynamic element of community practice to tertiary cancer center is not something that we expected nor our partner expected. So I won't make any equalization about whether that will repeat in head and neck cancer. It will not because that situation is not existing in head and neck cancer. Doesn't mean that there is not competition. But again, we are behind VP1016. We think based on the data that we have released. We are still awaiting the final data set release, but that will be released in a scientific publication. But as we have also indicated, you have in essence seen the data based on the interim data because we have communicated that closely, mirror that interim data. that we are well positioned to compete about patients and recruitment in the settings where we strategically have placed AB1016.

Thank you.

Next question today is coming from Alexander Kramer from ABGSE. Could you elaborate on a potential timeline to market for the locally advanced cervical cancer setting? Also thinking about potential to accelerated approval, how do you see the commercial opportunity patient population in locally advanced cervical cancer compared to the CO4 setting?

I can start answering the question bottom up. It is a larger patient population. I do not have the exact number on top of my head. but it is a significantly larger patient population in the locally advanced. That is obviously a driver. The driver is primarily patient need. And as I said, we regret that we are not capable of positioning our vaccine in recurrent metastatic cervical cancer because the patients there have an unmet need, as patients do have an unmet need in locally advanced cervical cancer. But if the question directly on the commercial opportunity, then yes, it is a big opportunity in the locally advanced setting. I am not going to give you a date for when we expect to have definitive data in locally advanced. I did allude to the fact that we are 99% ready with the design. We need the last elements. And I also alluded to the fact that we are obviously bluntly aware that an interim analysis that can give a meaningful guidance is needed without jeopardizing the final results. I will be happy to guide on exact timelines when we have announced the final design, which is imminently.

Thank you.

Our next question today is coming from Auburn Ascender from Carnegie. Can you explain how the different factors were ranked in the decision to discontinue VBC04? Was the main reason the commercial potential or did scientific evidence showing better results in earlier stage disease carry more weight? And there is a sub to this. How far are ongoing programs sprung out of the autoimmune platform from being partnering ready?

Yeah, I will deal with the first part of the question and make sure the second part. I think I already answered it. The commercial element did not pay any part in the decision making. As I said, we are driven by the unmet need. And the unmet need is existing and recurrent. It exists in locally advanced. So, yes, the locally advanced will be a bigger commercial opportunity, but that was not the factor that was involved in making the decision. It was purely feasibility decision that we did not feel that it was the right way of spending NICO resources and money on something where the fast-to-market elements lost fast. And that was number one driver. in essence, only driver for the decision-making.

And then I can add on the autoimmune platform program. So they are, as you see, with quite frequent updates moving forward at good speed. As we are speaking, there are multiple experiments running. We are in contact with a lot of potential partners here already. This is a field that is of interest for big pharma, and we've also seen a deal at the preclinical stage in the same space coming in the last six months. So whether or not it's partnering ready is always a definition as to what we want to see and what a potential partner wants to see. it is not unlikely that there would be an opportunity to partner some autoimmune disease programs at an early stage. And I think we have alluded to already a year ago that this is a platform, and we will continuously evaluate the best partnering strategy for this system, also in the past with the oncology platform.

Thank you. We've reached the end of our question and answer session. I'd like to turn the floor back over to Michael for any further closing comments.

Thank you very much, Kevin. I'd like also to thank my colleagues here and all the participants dialing in to this call this afternoon. We look forward to keep you updated on the progress on all our programs. And with those words, I wish you a very good day.

Thank you. That does conclude today's webcast. You may disconnect your line at this time, and have a wonderful day. We thank you for your participation today.