Nykode Therapeutics AS (NYKD) Earnings Call Transcript & Summary

Greetings, and welcome to the Nykode Therapeutics webcast. [Operator Instructions] It's now my pleasure to turn the call over to CEO, Michael Engsig. Please go ahead, sir.

Thank you very much, Kevin, and a very warm welcome to everybody listening into this call here, where we will take you through the data from the final analysis of CO2, which we reported yesterday. I'm sure you sense from our presentation here that we are extremely enthusiastic about these results. Just a quick look at the forward-looking statement, which you're all familiar with, so quickly move forward. With me today, I'm very happy to have Agnete Fredriksen, our Co-Founder and Chief Business Officer; and Klaus Edvardsen, our Chief Development Officer, who will be taking you through the data and details. So just to frame today's presentation. What we're talking about today is the final analysis of the data from CO2, which was exploring VB10.16 in combination with atezolizumab in patients with advanced cervical cancer. And for those of you who have followed us also last year, we reported the positive interim results from this trial back in May and where, in particular, encouraged by the long durability of the responses and the long stabilization of the patients that we saw in those patients that had already stayed in the trial for some time at that time point. The big question for everybody was will this durability and stabilization turn into real survival benefit for the patients in the final analysis. And we are extremely happy to report that indeed, it did turn into a survival benefit with 16.9 months in the overall population -- and more than 25 months, meaning not reached for the medium overall survival in the PD-L1 positive patients, we can say that we have really demonstrated survival benefit here. The PD-L1 positive patient population is particularly interested -- interesting for us because that's the population that we will primarily target in the next development activities. The -- sorry, the overall response rate and the disease control rate that we saw in the interim analysis were confirmed. But again, we are intrigued by the PD-L1 positive sub population where we saw an ORR of 29% and a disease control rate of 75%. The favorable safety profile that we saw in the interim analysis were confirmed. And that's important not only for the patients and the women in this trial here but also for the product candidate, again, with a thought to the target populations where we intend to develop this product. For those who are interested in the translational science, again, we saw a very strong correlation between the antigen-specific immune response and the associated clinical outcome, which is important for any therapeutic cancer vaccine that you want to develop and bring to the market. So again, we think these data are unique and very strongly indicates the vaccine effect. Now there is a subpopulation that we are also very interested in. That's the one called PD-L1 positive with one prior line of systemic anticancer treatment. That's because the next trial that we intend to be running in advanced cervix cancer, we'll be targeting a population that is very close to this one. And here, we saw, but I'd like to characterize the mind-boggling progression-free survival of 16.9 months overall survival, median overall survival was not reached, so more than 25 months and ORR of 40% and control rate of 80s decease %. So in together, we find these data strongly indicates a differentiated and long-lasting clinical activity of VB10,16 in combination with atezolizumab compared to what you would expect to see with the checkpoint inhibitor therapy alone. So just a quick introduction to the company for those of you who are new to Nykode. Nykode is a clinical-stage immunotherapy company. We are entirely dedicated to leveraging our unique and proprietary vaccine technology platform, which you need to target antigens to antigen-presenting cells, which in turn generates a strong CD8 T cell response, which has been shown to correlate with clinical responses in solid tumors. Now the technology is modular in its buildup, which gives us a large degree of versatility and flexibility. That means that we can easily incorporate new antigens and adapt the product to new diseases. -- across oncology and infectious diseases and autoimmunity. We are very dedicated to advancing our wholly owned lead assets in '16, which we're talking about today. And today, as we mentioned, we'll be reporting the final data from the CO2 trial, we'll be focusing a lot of today's presentation on durability parameters, but we are -- have also announced that we'll be starting a potential registrational study in advanced cervical cancer, and we'll initiate that trial towards the end of 2023. And we are expanding this program into head and neck with the start-up of CO3 trial in the first half of 2023 trial that we're running in collaboration with Merck, who is supplying the KEYTRUGA. In Nykode, we believe in partnerships. We've entered a number of partnerships, including 2 game-changing out-licensing deals with Genentech and Regeneron. The company is well capitalized with a cash position of more than $200 million at the end of fourth quarter, which fully funds all the activities that you'll be hearing about today and takes us well into the next couple of years. Now with those words, I'm going to hand over to agenda, our Co-Founder and Chief Business Officer, to take us and through a short recap on the technology platform.

Yes. Thank you, Michael. So BT is based on the platform technology, as we call the back-to platform technology that uniquely targets the antigens to Andean presenting cells. We've so far chosen to work with the plasmid DNA format. We also have IP for making this unique Vaccibody molecules in other vector formats like mRNA, viral vectors or recombinant proteins -- but the products we have in the clinic today is on purpose made on the plasma DNA backbone. And the unique thing with the [indiscernible] molecule is that we have the antigen linked through a dimerization unit to a targeting unit that find specifically to a certain important cell type called antigen-presenting cells, which is very important in order to trigger an immune response. This is also the way we can make sure we control the immune response to the immune response with different directions. And by choosing the targeting unit of choice, we can direct the immune response into the profile that is desired for specific diseases. We go to the next slide, please. So for VB10.16, plasma DNA-based vaccine simply formulated in PBS, we delivered with a media free get injector that makes sure that the DNA plasmid is transacting cells in the muscle, and these muscle cells starts then to produce and decrease the vaccibody protein. Since the orange part with a targeting unit that is unique for the [indiscernible] is an inflammatory chemokine. It's first important feature is to attract the specific cell-type called antigen-presenting cells where all antigens needs to be delivered to these cells in order to initiate an immune response. So we make sure that, that happens more effectively by having the antigen presenting cells, infiltrating the muscle and ending up as the neighboring cells to the sellers producing constantly new vaccibody proteins. When it binds -- it will be internalized in signal, and that's the other important feature of VB10.16 and other products based on the same platform is every molecule we make for the same targeting unit will be taken up into the cross-presentation pathway, and that's the way we control that the immunosensors to the antigen is primarily a strong and broad CD8 T cell response and not only focused on CD4 helper T cell responses, for instance. And in these CD8 T cell responses that can go and recognize the antigens in the tumor. So all tumor cells have expressed the antigens we have in the vesting will then be recognized by the CD3 cells and be able to kill them. This principle, we employ among different products. So if you go to the next slide, our rich and diversified pipeline is based currently on the same format with the same targeting unit and the same dimerization unit and all on the plasmid DNA backbone so far, which means that the products you see here covering products within the off-the-shelf oncology vaccines as well as individualized personalized cancer vaccines that we work with together with Roche Genentech, they all use the same platform technology. So you could also be pretty confident that the data we show you today with VB10.16 has transferability across to other programs that we developed together [indiscernible] and Genentech and also future products that we will take into the clinic ourselves. Next slide. EBIT 16 specifically has this particular targeting unit with the CCL3L1 unique chemokine [indiscernible] unit and the antigenic unit we have incorporated the following HPV-16 E7 6 antigens. HB6 is the most prevalent oncogenic HPV string, so an important target, and it's wholly owned by Nykode, not affected by any of the partnerships that we have so far. So let's see how this performs in cervical cancer patients. And I'll hand it over to Klaus to get through that.

Thank you, Agnete. Let me just remind you all that the cancer is driven by HPV, and specifically here, obviously, HPV16 because that's the vaccine construct that we have been utilizing still significant. The major cancers driven by HPV is head-and-neck in cervical cancer, and then there is a number of minor indications that are although important, I will come back to that towards the end of the presentation. Just for the unmet need, especially if you look at advanced cervical cancer, female diagnosed with that will very unlikely be alive 5 years after that diagnosis. There is a desperate need for new treatment paradigms and modalities in that setting. One could obviously speculate that based on the prophylactic HPV vaccine that we would be looking into a diminishing number of cancers with HPV driven. The background, that's not the case. There is an expected increase over years to come in those cancers. -- and that's obviously likely because of a limited uptake or not a full uptake of the prophylactic vaccine and obviously, the fact that nonprophylactic vaccine will be 100% efficacious. Next slide, please. Just a few words before I actually go into the actual data. What would be considered good in such a setting, meaning what would be competitive, what would actually offer a different treatment possibility for female with that cervical cancer. To do that, we have listed the treatment options that potentially all dependent on geography would be available for female in that cancer type. That's chemotherapy. It's one of the checkpoint inhibitor, KEYTRUDA, pembrolizumab, [indiscernible] and then Logan the block Tita that I will come back to at late. -- what patient population would have to be the relevant comparator is obviously from a checkpoint inhibitor perspective, the PD-L1 positive patient because every trial would be enriched for PD-L1 positive patients, obviously, based on the motor action. So in that setting, and I not want to read out the underlying media either the medium PFS for each of those 4 treatment modalities, but just to point you to the fact that to be competitive with another treatment in this setting, you would like to see a median above 4 months and a media mobile survival above 14 months. Next slide, please. Just some words about the trial, BBC02, a single-arm trial, testing up the concept of adding the HPV-16 vaccine 116 on top of the checkpoint inhibitor at [indiscernible] in patients with advanced surgical cancer. The primary endpoint for the trial was safety and overall response rate assessed by RECIST by an independent blinded review. The key secondary endpoint duration of response, progression-free survival, overall survival. And then as Michael already alluded to, is obviously critically important that when you utilize a vaccine approach that you can actually show that you mount and your response in the patients who do vaccinate and we will show you some preliminary data here because you have to bear in mice that you see the analysis of this data set as a relatively fresh off the press. I can then turn you to the interim analysis for a more comprehensive analysis of using it at this stage. The trial was conducted in Europe in 6 European countries, it grow 52 patients. The treatment setting here was a nearly 12 months vaccination period where we were starting with a vaccine induction giving 5x every 3 week followed by a vaccination maintenance saving, where 6 vaccination was given every 6 weeks. That was all concomitantly given the atezolizumab that was given every 3 weeks. It was followed by a 12-month follow-up period where in essence, patients would have had an option to continue on that [indiscernible], very few patients did continue on atezolizumab to be specific for patients. That is an important element also to bear in mind, when you try to compare this data set in a [indiscernible] to what you would expect in a monotherapy checkpoint inhibitor setting. Next slide, please. A few words on patient disposition. I'm not going to spend many words on it because in reality, what you see is what you would expect from a patient population with advanced stage cervical can. So there is, however, one important point to pay attention to and that is the fraction of PD-L1 positive patients enrolled into this trial. As you can see, it was a little less than 0.5 48%. That's, again, an important parameter to bear in mind when you do the comparison to monotherapy checkpoint inhibitor treatment in a similar setting. Next slide, please. Safety, as already alluded to, it was very well tolerated. You could say in conclusion, and I can start with that. that you're not seeing much additional adverse event to what you would expect from atezolizumab or any checkpoint inhibitor for that matter in this setting that can be seen on the left on the slide where our investigator assessed adverse events attributed to the vaccine has been listed. You see those numbers are relatively small, and obviously, all might to moderate. If you look to the right on the slide, you would see that the combined assessment of adverse event was that an adverse event was seen 67% of the patients, they were primarily it moderate in great 1 to 2 with very, very few patients experiencing anything above that. No serious adverse events were reported related to B106 the vaccine, and there were no that's related to either VB10.16 nor [indiscernible] in the trial. Next slide, please. Let me just draw the key headline results with regard to duration endpoint at this slide, and then I will subsequently get back to all of the clinical endpoints later in the presentation. As you can see from the table, we were uptaking strong and durable antitumor efficacy across all patients reaching a media-vie survival in the overall patient population of 16.9 months. If you look into the PD-L1-positive subset of patients, which is obviously the relevant comparator to the checkpoint inhibitor monotherapy, the medium overall survival was not reached, but at this stage would be at least 25 months. Media PFS in a similar -- or a similar setting PD-L1 positive, was 6.3 months. So let me just stop and compare back to the contextualization slide where I was indicating that you at least would have to meet the median PFS of 4 and an overall survival of about 14% to become relevant. I think it's fair to say that, that has been met and that you, by no doubt, can claim that you see a vaccination effect, although you cannot say that in a statistical sense as it is at single [ uptil ] but no concern claiming vaccination effect, you're not doubling these 2 parameters from what would be expected from a checkpoint inhibitor monotherapy no. Next slide, please. Just a few words on the observed overall response rate in the overall patient population is 19% with a disease control rate of 60% disease control rate in this setting, meaning that patients derive clinical benefit without actually obtaining resist criteria response, which means that you would need a tumor reduction overall of at least 30%. In the PD-L1-positive patient segment, the overall response rate was 29% with a disease control rate of 75%. If you look at the waterfall plots to the bottom of the slide, overall population to the PD-L1 positive to the right, you are obviously seeing the depth of the responders. You are seeing the stipulated [indiscernible] minus 30% RECIST criteria response -- the important take-home message otherwise from the waterfall projects that you see a significant proportion of patients that do derive clinical benefit, meaning they get a reduction in tumor size, they just do not get a reduction to the minus 30%, but some of the patient gets very, very close and we can return to the reason for that in slides -- next slide, please. Looking at the spider plot at individual patients. We have broken that down so that it does not look too much like again to responders in the red and non-responders in blue. And if you look to the far left on the deck, you see the non-responders in blue, you obviously see the non-responders. There are a number of patients that progress very fast. But you also see that there is a significant proportion close to half that is actually deriving benefit because you see a stabilization in almost flat curve from the time you start to see that flattening and then up to the full follow-up of the trial of 12 months. In the red color coded, you see the 9 responders and you see the late responses, and you see that they all except one patient keep that response for the duration of the follow-up period. We've also indicated to you the spider block for PPL 1 status, and I will only draw your attention to the phone right of the slide, where you see the PD-L1 negative patients. Number 2 responders, one complete response, you see that and then you see another responder that relapsed relatively fast in the red color coded. And again, here in the blue color code that you see patients that the right clinical benefits that are actually obtaining a resist criteria response -- we are just indicating here that obviously, on 2 responders on faster lapsing it is difficult to for a conclusion as to whether there is an effect of the vaccine in the PD-L1 negative patient segment. But if you link it to the stabilization, there is absolutely no doubt that you're also seeing clinical benefit in that patient segment, which is something that we would obviously also return to and try to capture some treatment option for a patient population like that, that is even higher on emit. Next slide, please. Just a few words on the patients that obtain clinical benefit in the sets of stabilization, again, meaning that they're not responders by RECIST, but they are certainly deriving clinical benefit -- if you look at it, we have only 8 patients that obtained disease control for gene of those patients completed the entire treatment vaccination program for the year and 7 out of those patients are still in follow-up without any dividends or progression. Next slide, please. Now to the Kaplan-Meier curves and the duration endpoint. We start with, obviously, the duration of response that is only assessed in the Kaplan-Meier curve on patients that do obtain a RECIST response, and that landed in the overall patient population at 17.1 months. If you look at the broken out PD-L1 positivity or negativity you see that it is still 17.1 months in the PD-L1 positive indicating that this effect is driven primarily by PD-L1 positivity, but you cannot as indicated on the spider plot -- say that there is no clinical benefit of treating patients with the vaccine in the PD-L1 negative patient segment. Next slide, please. Looking at the progression-free survival, it reached 4.1 months in the overall patient population. And again, as already indicated, if you look at the PD-L1 positive patient segment, the medium-tier GS landed at 6.3 months and not go well much on the medium PFS for the PD-L1 negative segment because of the relatively low number of patients that did derive a response in that patient segment. And now to the final duration endpoint overall survival, which obviously overall survivor is hold an important end point for obvious reasons. But clearly, if you are looking at patients with advanced cancer. It is likely not possible at that stage to cure any of these patients. So therefore, the critical element for patients obviously become how long can I live without having a burden that is too cumbersome with regard to either adverse event based on the treatment or of the tumor. And that overall survival in the overall patient population landed at 16.9 months. As already indicated, if you look at the patient's PD-L1 positive, the medium or survival has not been reached at this stage. It is at the current stage about 25 months and will obviously increase where it lands is not possible to say at this time point, it will, unfortunate to be only dependent on when patients are not any longer aligned. Next slide, please. As indicated, it is important to obviously claim a vaccine effect or a correlation between kind of vaccine effect on the clinical effect that you can indicate that you actually mounted an immune response against the entities that you did vaccinate against. As I said, we are in analysis not still for this data set, but we just thought that it was important to indicate to you that as we showed at the interim analysis that if you look at the higher T cell responses, you were seeing a strong statistical correlation between patients that actually did the right clinical benefit at a much higher spot count number than patients that did not have any clinical benefit the ones that did progress early. If you lump all of those responses together and look into the fold increase, same picture statistical significant in the patients that derive benefit and compared to the one that did progress. Next slide, please. Now just how do we put this into context? I think I have noted over the entire presentation to the fact that obviously, the compare here would be what would a patient be expected to do if you have been treated, the PD-L1 positive patients. And obviously, we look into the PD-L1 positive patient segment with regard to the checkpoint inhibitor because of the mode of action because those trials obviously would be enriched for patients that are PD-L1 positive and compare that to the patient segment where you have added the vaccine on top of a checkpoint in vein this case atezolizumab again, in the PD-L1 positive patient segment. If you look at KEYNOTE-158, that's the pembrolizumab trial that tested out in second line, and this Cipla in PD-L1 positive in EMPOWER 1 trial, you see a response rate of 17% and 18%, respectively, compared to ours 29%. And then to the medium PFS, 6.3 months in hours, 2.1% in Penton 3 months in [ Sepumab ], more than a doubling of the median PFS. And when you look at overall survival, I said not reached, but compared to 11 months and 13.9 months, respectively, in pembrolizumab and [ ziplimab ], more than doubling again of that significant import. The last part that I would like to draw your attention to is [indiscernible] as indicated on the conceptualization site, there is a new treatment option for patients that are failing first-line standard of care in the U.S., first-line standard of care in the U.S. is pembrolizumab cross hemotherapy. Those patients would have very limited options today because you would likely not rechange them with a monotherapy checkpoint inhibitor, you could rechallenge them or not rechallenge them, you could try to treat them with a different chemotherapy setting or you could try to treat them with [indiscernible] vedotin. One problem with that compound is that it is a black box morning, a significant eye toxicity associated with the compound. There are [indiscernible] in the optical nerve, meaning that some patients do go blind, and there are some significant observations in the cornea. But anyway, an important comparator to what you potentially could offer patients if we can get our vaccine register, which we have every intent to do, obviously, not based on this trial, fun based on the future program, it was back up very well to Tia which obtained a 24% response rate obviously PD-L1-agnostic because it's a different mode of action and a medium PFS of 4.2 months in the medium oval survival of 12.1 months. Next slide, please. Here, Michael alluded to it in the executive summary, and we are only giving you this slide on the data here as a prelude to our potential registration effort that I will come to on the next slide is to look at patients that do fail the first-line standard of care in the U.S., as I indicated, would be PD-L1 positive patients because they have -- will be giving [indiscernible] chemotherapy plus minus [indiscernible], and they would have failed only on systemic anticancer therapy. If we look at that patient segment in our CO2 trial and with the caveat that this patient segment here, they are CPI is because they were enrolled in Europe. But if you look at the numbers, they are pretty compelling and overall response rate of 40%, a CR rate of 13% and nearly all female obtaining clinical benefit with a disease control weight of 80%. Medium duration of response days at 17.4 months because it is primarily driven, as said by PD-L1 positivity. Medium PFS increases to 16.9 months and medium-value was obviously not leased in that segment either. Next slide, please. I'm now going to go over details on this slide. We have in essence a December update represented to you, our future clear plans. I just want to draw your attention to the COI Phase II cervical cancer trial, which is our potential registration program in patients that do fail first-line standard of care in the U.S. That trial is going to be conducted by the [indiscernible] quality group that is the [indiscernible] group in the U.S. that everybody would like to conduct that why with. They don't [indiscernible] every approval in gynecological cancers in the U.S., and they will conduct this trial on our behalf. We expect that trial to open for first patients enrollment before end of this year. I will have to say that there are obviously ongoing negotiations with FDA as to the usability of that design for a potential registration because as already indicated, CO2 enrolled patients that are CPI naive. Here we are talking about patients that will be CPI refractory. We will obviously not pick patients that are primary refractory and could likely not risky rose for patients that are secondary refractory, meaning that they have to write a tumor shrinkage, those data in CO2 would be kind of indicative as long as you can obtain any type of clinical benefit, thebaine can prove on and keep that benefit for a substantial period of time. That's the hypothesis that we're going to test in CO4. We will not spend all money upfront. We will do it adaptive. We roll a subset of patients. We have indicated 30 patients look at whether the signal is strong enough and then enroll up to 100 patients, which is kind of standard for an accelerated approval in this setting and exactly the conduct that Tiple used when they obtained their accelerated approval. Let me just finalize on future plans that the more critical important elements and the likely most important take-home message from the CO2 data. That is, as I already indicated, if you can get any tumor slippage, whether it's RECIST response or a disease control, what the data in CO2 indicate is that, that responds or stabilization, if you like, can be kept and it can be kept for a significant period of time. I think that has been indicated by the duration endpoint. And again, do remember that we only vaccinated for 1 year. And we only gave that to reason after the waste majority of patients for 1 year, you would normally have extended to 2 years based on the safety profile that's likely nothing that prevents us from doing so in the future. So where are we looking where we believe that that would almost be a waiter but is in the adjuvant setting. The adjuvant setting means that you have already treated patients upfront, and you select patients for benefit, meaning they have a swath of their tumor and then to keep that shrink, which you use an adjuvant treatment kind of like what you see and what I just described would be a significant benefit with that action -- why can you ask do you not start in locally advanced adjuvant because standard of care in that setting has not yet been established. There is an ongoing trial that is indicating whether it is good to add pembrolizumab of top of standard of care in that setting, and we are even awaiting the outcome of that. I think it's important to mention here that we are already in collaboration with Merck on head-and-neck cancer program where they're looking for a dose escalation, and it will obviously be very natural to continue that collaboration with Merck as soon as we have established standard of care, meaning will it be beneficial to add pembrolizumab to standard of care, then we will add the vaccine and drive an even more prolonged duration of responses that port. Next slide, please. Here is the concluding slide on the data set that I have just presented. I have -- I think I have read out those numbers so many, many times. I'm not going to do it again. I'm just going to say that not unexpectedly, that I think this data set is very strong. It is, in my mind, a very clear indication that you can actually talk about vaccination effect that is not attributed to the eculizumab component of the efficacy and the results are so encouraging that we will have to fight fast way to get this compound available to people with a significant open with a significant unmet medical need. I think I have only one slide left and that is, of course, to acknowledge the patients, their families and the investigators that took part in this trial if they have not been willing to do so, they would obviously not have been in a position to present any of the data to you today. So thank you to all of those. And also thank you to Roche for providing a [indiscernible] to conduct the trial. Let me just finalize it all by putting a few words on what is the market potential. I already indicated that at the first slide. Now just to put it into the full context when we have described our future plans, we will look into the cervical cancer in the second line, the one take fail first-line treatment that is indicated. We very clearly look into the adjuvant setting also in cervical cancer, although we locally advanced -- and I've briefly mentioned the options in head and neck cancer. And then as I indicated, there are other HPV-driven cancers. They are smaller indications. But if you lump them together, it becomes a reasonable patient number. And obviously, it's not only about patient number, it is about unmet need. And those patients have a significant one that angulation and tile cancers. And our intent is to capture all of that patient segment, which at this stage is approximately 130,000 new cases driven by HPV16 in the U.S. and 5. And by that, I hand the presentation over to Agnete.

Yes. Thank you, Klaus. So today, we as the focus. It is part of the platform technology that we are developing in nice -- and as you see on this slide, Michael, is more than we can. We befalls under the category of ABC-specific antigen delivery and stimulation products within cancer immunotherapies. We can develop more products that are based on the same platform, which we are already doing, for instance, with the personalized vaccines together with Genentech and off the shelf vaccine [indiscernible] as well as internal products. Then we can use the same platform to stimulate the immune system for infectious disease purposes, either in the direction of these unique T-cell responses that we see here are more in the direction of other immune response profiles like antibody responses, et cetera. We can also utilize the technology with certain twists with the targeting units, particularly so that we can make sure that we are inducing an inhibitory response and downregulating response antigen specifically, which is what we would want if we develop products to treat autoimmune diseases and, for instance, also allergy. So that's an interesting future potential with our technology that's based on what you've seen today with certain modifications. Then we will not restrict ourselves to that as part of the name Michael New code means that we can also use our in-house competence to build in additional modules, now combinations and structures. We can also go beyond [indiscernible] and [indiscernible] therapeutics with these new codes that we can do specifically my post. Next slide, please. So just an example with building in additional molecules. So we have already demonstrated as the last year that we can further improve and control the immune response by building an additional port module in the patina backbone that decreased separate cytokine, and this is something we can do also with the fixed module and essentially even fixed modules in the future. And by doing this, we can even further control the immune response. In these figures, you see we already see an enhancement in T-cell responses and antitumor efficacy for applications within cancer vaccines. And if we move to the next slide, that is also a potential we can use for infectious disease, purposes to cater enhanced antibody responses and/or control it in different directions. And for immune tolerance, we find here that our technology is very well suited to provide a unique and very specific approach to control the immunome, both through the targeting units that we can specifically design to both induce but also make sure that the antigens are targeted to certain subtypes of engine presenting cells in order to induce regulatory T-cells that can down regulate response an specifically. And here, we can also play with the port module technologies. -- please go to the next. So as we sum this up, we focus today on immune stimulation for cancer. And here, the platform really can show its potential by just changing the antigen, we will expect the same unique [indiscernible] profile that we believe we've also shown here to date and using an immunome that correlates with clinical efficacy. So we are very excited to also move that into further products. And then we have a lag in infectious diseases as well as what I explained for immune tolerizing vaccines. And then again, with the name of NewCo, we think also that in the future, we can further employ our ability to create novel structures and use that as therapeutic proteins also the on-rate. So then I hand it back to you, Michael, for listing [indiscernible] the future and the finances.

Thanks, Agnete. Thanks, [indiscernible]. Just 2 more slides. First, the outlook. And as you all noticed today, we announced the positive data from the CO2 trial, which has been an important milestone for us, but we will mediate start focusing also on getting the CO3 trial, our expansion into head and neck started. We are planning to enroll the first patient in the first half 2020 as well as the CEO 4 trial, the potential registrational trial, which is our next step into the advanced cecal cancer. We plan to start the trial and move the first patient in the fourth quarter 2023. We will also, as to by Klaus, be updating the survival data. So very importantly, today was the final data of CO2, but we still have patients in the trial or following patients from the trial. So we will be able to provide updates on survival when we get to the first quarter of 2024. And then we'll be updating the market on the autoimmune program in the third quarter of 2023. I A few words on the financials. As I said in the beginning, we are well capitalized with more than USD 200 million at the end of fourth quarter last year, which will fund all the activities that we described to you and run us probably get into the future. We also reiterated our statement that [indiscernible] is continuing to explore a potential listing at the NASDAQ total market in the United States. And with those words, I think we can open up for questions, operator.

[Operator Instructions] My first question is, you mentioned results from subpopulation of PD-L1 positive patients with 1 prior line of systemic treatment, 40% ORR and 80% ECR. How large is the subpopulation in your study?

It's a fair question. And it is 16 patients, as I also alluded to, it's not part of the formula analysis. It is a prelude for you to get an understanding of why we do believe that there is a likelihood to see a positive outcome in the CEO for trial, again, with the caveat that I also very clearly stated that there is a difference between CPI-naive and a secondary CPI refractory patient population, but that's the context that the presentation should be seen...

[Operator Instructions] We'll have over further questions. If there are no further questions, I'll turn the floor back over to management for any further or closing comments.

Very good. Thank you very much. And once again, I'd like to say thanks to everybody for dialing to this call here and looking forward to keep you updated on the progress in the future. I wish everybody a 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.