Hello and welcome to the Nykode Therapeutics first quarter 2023 earnings conference call and webcast. If anyone should require operator assistance, please press star zero on your telephone keypad. A question-and-answer session will follow the formal presentation. You may ask a question at any time 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 turn the call over to your host, CEO Michael Engsig. Michael, please go ahead.
Thank you very much, Kevin, and a very warm welcome to everybody on the call this morning in Norway and Scandinavia. We're gonna run this one here for our entire audience, including also the international. We're gonna run it in English this morning here. Just a quick look at our forward-looking statements. As usual, we assume that you're familiar with these statements. We'll quickly move on. Again, as usual, I am happy to inform you I'm joined here today by Agnete Fredriksen, our Chief Business Officer and Co-founder, as well as Harald Gurvin, our Chief Financial Officer.
I will take you through, both a highlight level of the data that we presented in this quarter here, as well as of course a deep dive into the financial reports that we announced this morning. For those that are new to Nykode, a quick at a glance introduction. Nykode Therapeutics is a clinical stage immunotherapy company entirely focused on exploiting our unique proprietary immunotherapy platform, which uniquely targets the antigens to the antigen presenting cells, which in turn generates a strong and broad CD8+ killer T-cell response, which we've shown to be correlated with clinical responses in solid tumors. Our technology is modular in its construction, which gives us a high degree of versatility and the ability to easily incorporate new antigens and adapt the molecules to new disease areas.
We've expanded our focus from oncology over in fixed diseases and are taking the first steps into autoimmunity. We are dedicated to invest and rapidly advance our wholly owned lead asset, VB10.16, which is an immunotherapy for HPV-16 driven cancers. We reported the final positive data from VB10.16 VB-C-02 trial in the past quarter, which again showed unprecedented and long-lasting survival benefit in advanced cervical cancer. In addition, we've announced that we'll be starting up a potential registrational trial in advanced cervical cancer. We'll tell you more about that in a couple of slides. We'll plan to initiate this trial in 2023 in the fourth quarter, we've announced that we are expanding this program into head and neck, another cancer type that are driven by HPV-16 virus.
We'll be doing that in the C-03 trial, which is a dose escalation study where we are collaborating with MSD, who will be supplying Keytruda. Nykode believes in partnerships. We've entered a number of partnerships including two transformational out-licensing partnerships with Genentech and Regeneron. We are well capitalized and this morning reported a cash position of $186 million at the end of first quarter. This quarter, including the data we announced after the end of the quarter, has in essence been very transformational for.
Please stand by. We're experiencing technical difficulties. Please stand by while Michael reconnects. Ladies and gentlemen, please do not disconnect. Please stand by when Michael reconnects. Please stand by. Once again, ladies and gentlemen, we are still connected. Please stand by. Do not disconnect. We're just waiting for Michael to reconnect. In the meantime, I'll turn the floor over to Agnete.
Yeah. Since Michael lost connection, I can continue from here. Yeah. For the highlights of this first quarter, including the subsequent important events, we do have the very important planning of the VB-C-04 trial, which includes a tight collaboration with the Gynecologic Oncology Group GOG Foundation . As we've said before, it's very important for them, for us to have them on board on this trial, and it's also important for the opportunity of this trial reading out and being performed in the optimal manner. We're very encouraged by having GOG on board. We also presented additional immunogenicity data from our fully personalized cancer vaccine program that we can go into in more detail today.
These were presented at the AACR earlier this month or last month. As Michael mentioned, the extremely important data that we have from the final analysis of the VB-C-02 trial, which is a phase II trial where we tested VB10.16 in combination with PD-L1 inhibitor atezolizumab in advanced cervical cancer. We'll briefly review these important data with you today. I can move on with the neoantigen data. Just as background information, just to remind you that Nykode is operating in this space of fully personalized or truly individualized cancer vaccines. This is really the program where we are custom-designing and manufacturing one vaccine per patient based on each patient's cancer-specific mutations.
In this field, there's been recent positive data by the Moderna-Merck and also recently by BioNTech. BioNTech actually had a paper published yesterday from. Both of these studies are then in early stage adjuvant settings, which means when patients have undergone surgery, and then they are treated in order to prolong or prevent recurrence of the disease. Nykode is importantly one of the first companies that entered the clinic with an individualized cancer vaccine. We did that with the trial that we call the VB-N-01 trial, where we dosed the first patient in 2018. We have presented previously positive data from this trial in, and it's running in multiple indications.
Importantly, different than what we see with the recent Moderna, Merck, and BioNTech data, is that this study is in CPI-experienced and advanced metastatic setting. Also looking a bit on the technology for VB10.NEO, before we move into the data. VB10.NEO is a trial that requires also bioinformatic competences, because this is a trial where we take a biopsy sample and then, sequence the biopsy from the tumor and compare that with healthy cells from the same patient, and also link it to that particular patient's HLA molecules, which are important molecules that present these mutations that are tumor-specific to the immune system.
In order to succeed in this field, you need to have strong in-house bioinformatic competences that can select the optimal neoantigens that could induce an immune response in each patient. Nykode has used quite a lot of resources in order to enhance our bioinformatic competences from before we started this trial. We have trained our bioinformatic pipeline on our own data and also linked to our proprietary Vaccibody technology platform that induces a uniquely broad and CD8-dominated immune response that you heard before. We train our algorithm in order to make sure that we capture these particular neoepitopes that gives us the particular and interesting immune response profile.
Importantly, we also focus on not just selecting the most immunogenic neoepitopes in a patient, but it's very important for us that these are clonal and clinically relevant, meaning that we try to select neoepitopes that are relevant for the patient. If we are able to induce an immune response to these, that they will actually be able to translate into clinical responses. We have presented before that we have a very nice correlation between what we call high-quality immunogenic neoepitopes that really take these factors into account, and they correlate with clinical responses. We, the data that we have, and importantly for the immunogenicity but also early clinical efficacy in the first patients, they are importantly in patients with 1- 4- prior lines of systemic treatment.
This is a different patient population than the adjuvant setting. These patients have then normally failed surgery. They have then recurred from that first treatment and undergone then at least one line of systemic treatment before entering the trial. They were all experienced checkpoint inhibitor experience when entering into the trial. I think it's important these days also for making and manufacturing one vaccine per patient that Nykode do have the IP for making vaccines on in different formats and formulations. We have so far focused on the DNA plasmid format, and that is a very generalized manufacturing process which is an intermediate in the mRNA and the viral vector production.
Just by knowing that fact, it should be more rapid, cost-effective, and robust, which is important when you want to manufacture one vaccine per patient. So far, that's also led to 100% manufacturing success rate to date, when we have identified a sufficient number of neoepitopes. With the DNA platform across all trials, we see that it's safe and well-tolerated. For our program, we have two studies for the neoantigen vaccines that we call VB10.NEO. VB-N-01 is the trial that we initiated before entering the deal with Roche and Genentech in 2020. This is where we dosed the first patient in 2018, and it's in combination with different sets of checkpoint inhibitors.
Five different indications, recruitment is finalized, and we have announced positive interim data at different time points. We can go through the data a bit more in detail. VB-N-02 is the trial that we initiated after signing the deal with Roche and Genentech. This is where we do dose escalation, also based on the safety profile that we've seen with the 3 mg here dose. We are increasing the dose up to 9 mg in the study, then it's in control combination with atezolizumab. This is then in more than 10 indications, and this study is ongoing. Just brief recap on the data that we have released earlier from this trial. I think it's important also in light of the recent data from other players in the field. We actually do see a response in all patients.
100% of patients across all 5 different indications did show a response to at least 3 of the neoepitopes. On average, 53% of the neoepitopes were immunogen-genic, and that ranged from 3 and all up to 20 neoepitopes in some patients. We feel that this really supports the broad immune responses that we also see when we compare preclinical trials. We've also shown this before. We see that the multiple vaccinations, over time we can just continue to increase the breadth and also the magnitude of the responses.
It's also important that when we can continue to dose the patients over time, we don't see that is a detrimental effect on the immune responses, rather the opposite, which is important for us when we move into the future, and I think it's also relevant when you're looking to the VB-C-02 trial data, sooner that Michael will go through. This data that you see here, with the tumor mutational burden, that's new data that were presented at AACR.
We believe these are important not just for this trial, but looking into patients as to the number of mutations that you find present in their cancer cells, which reads into this tumor mutational burden parameter, is important because we know that checkpoint inhibitors by themselves do have a higher likelihood of providing clinical benefit in patients with high tumor mutational burden. But in when we use a vaccine, we identify then up to 20 neoepitopes in these patients and select these. These data indicate that we see very strong immune responses also in patients that have very low tumor mutational burden, meaning that we are able to select neoepitopes that are immunogenic also in these patients and make sure that we can increase the immune responses to these fewer number of neoepitopes.
That is important in order to evaluate the likelihood of VB10.NEO being applicable in patients across the entire range of tumor mutational burden. We think that these data supports that VB10.NEO can have applicability in different cancer types. In this slide we also present some new data. So far the immune response data that you've seen for VB10.NEO has been focused on immune responses observed in the blood of the patients. We have now also been able to evaluate the T cell responses in the tumor of some of these patients in detail.
We are very happy to see that these T cell clones that are expanded in the tumor, we can also find them in the blood, and the T cell clones found in the tumor is also expanded in the blood. It really indicates that these vaccine-induced neoantigen-specific T cells that we trigger with VB10.NEO in the periphery or in the blood is also able to infiltrate the tumors, which is likely when we see this nice link between immune responses and what we will see is important in order for this to translate into clinical efficacy.
This last one I just want to repeat, because this is important for our vaccine platform and the differentiating factor of our vaccine platform to what we've seen with other vaccine platforms that also in the clinic, we did in this study, we had the ability to evaluate in detail whether the immune responses to each neoepitope in some of these patients were CD4 or CD8 T cells. In the majority of these patients, we see is really a strong and really dominating CD8 T cell response. We see CD8 T cell responses to neoepitopes in anything between 53 and 100% of the neoepitopes, actually being able to induce a CD8 T cell response, which we believe is very important in order to provide clinical efficacy.
In summary, for VB10.NEO, we've seen across all the patients that is generally safe and well-tolerated, and this is in patients with advanced cancer and multiple different indications and late stage, so they've undergone like 1- 4- prior lines of systemic treatment. The vaccine-induced T-cell responses are broad and also importantly long-lasting that we believe is important for this long durable efficacy that we also can see and observe in the VB-C-02 trial. The majority of neoepitopes that we see induce these polyfunctional CD8 T-cells, and it's really the type of immune response that we believe is most important for providing clinical efficacy.
Now we also added that these T cell responses are elicited both in TMB high and low patients, which support the potential in this broad range of cancer indications. As we hope and expect, but important also to be able to show that the T cell clone analysis in tumor and blood indicate that the vaccine induced neoantigen specific T cell responses that we have observed in the blood are actually able to infiltrate the tumors, which is where they are important in order to provide clinical efficacy. I think I'll hand over and back to Michael, if you're back.
Excellent. Thanks. I'm back. I hope, Agnet e. Thanks a lot. I apologize for that interruption. I'm afraid I managed to kick myself out of the call. Thanks for taking over, Agnete , and perhaps we move on to a quick run through of the data we announced with VB10.16 for our VB-C-02 trial. Let me again just emphasize that we feel these data were indeed transformative for Nykode, not only for the VB10.16 program, but for the technology platform as such in terms of the validation it gives to our Vaccibody construct and the approach of targeting the antigens to the antigen presenting cells. VB10.16 is our therapeutic cancer vaccine against HPV-16 driven cancer types.
It's basically built, like, you know, the Vaccibody with a targeting unit, a dimerization unit, and then we have incorporated the E6 and E7 antigens into the antigen unit. Again, also important to emphasize the program is wholly owned by Nykode. We have entered collaborations with partners, but we have not given away any commercial rights to this program. A quick look at the patient population. HPV-16 driven cancer types does represent a significant unmet medical need. The prognosis for in particular the recurrent and metastatic cervical cancer patients is very poor with a 5-year survival rate of less than 5%. Cervical cancer is a larger part of this, but it's not the largest or the only.
In addition to cervical cancer, we also see a large group of head and neck patients being driven by HPV-16 infection, in addition to a group of slightly smaller but combined still sizable type of cancer or cancer types, anal, vulva, vaginal and penile. In total, we are looking at approximately 130,000 new HPV-16 driven cancer types alone in the U.S. and Europe per year. When we look at the outlook for these cancer types, we, and you might hear us say unfortunately, are looking at increasing number of incidences despite the availability of prophylactic vaccines. That's in part due to a not 100% efficacy of these vaccines and probably even more because of a low uptake of these vaccines in certain parts of our world.
On a 10-year horizon here, we are looking at forecasts that shows a significant increase in the incidence, and we probably will continue to see an unmet medical need for decades into the future. A quick look at the trial design. VB-C-02 was enrolling up to 52 patients. It was run across 6 different countries in Europe and enrolled patients with advanced cervical cancer. The patients were put on a combination of VB10.16 and atezolizumab for 12 months, after which the treatment was stopped, and the patients were followed for additional 12 months. This slide here gives you a perspective on what we think good would look like before we show you the results.
It's always an interesting challenge to try to figure out what compares we should compare with when we try to judge whether these data were good. In this slide here, we show you the main parameters, median overall survival and median progression-free survival for chemotherapy, which is historically the first line treatment. We show it for the two checkpoint inhibitors that have published the results in the PD-L1 positive subpopulation. The reason why we focus on this subpopulation is because that's the subpopulation that we will be focusing our development program on in the future. For Keytruda and Libtayo, you see median overall survival ranging from 11 months to 13.9 months and median progression-free survival from 2.1 months to 3.0 months.
Very much in the same ballpark. This is where we feel checkpoint inhibitors would end up in a monotherapy in a PD-L1 positive population of patients with advanced cervical cancer. We also show the published results for Tivdak. They've reported median overall survival of 12.1 months and median progression-free survival of 4.2 months. The reason why we show Tivdak here is because that is the product VB10.16 would likely go into a competition with in the patient population that we are targeting. The conclusion is, before we look at the results, that anything in terms of median progression-free survival over four months and in terms of median overall survival of more than 14 months would constitute a very good result.
Quick look at the patient disposition, this disposition looks very much like you would expect from a trial enrolling patient with advanced cervical cancer. There are two things that I'd like to draw your attention to here. One is the PD-L1 positive distribution. Here you see slightly less than half of the patients were PD-L1 positive. If you were to go out and do a random sampling of the population, you likely would see a larger proportion of patients being PD-L1 positive, we tend to see the historical data somewhere in between 70%- 80%- 90% of the patient population. Another data point here is the median age, 47.5. Importantly, this is not a group of very elderly patients.
This is unfortunately women who are in the prime of their age, looking forward to start enjoying an active life without the kids, and have many years on the labor market still. Quick look at the results here. We show these results on this slide for all patients and the PD-L1 positive group or subpopulation. Just want to draw your attention to the lower parts of the table here. Median progression-free survival for the all patients group was 4.1 months, and for the PD-L1 positive population was 6.3 months. Median overall survival for the all patients group was 16.9 months, and for the PD-L1 positive was not reached, which means estimated to be more than 25 months.
If you compare that with our slides that was trying to put into context what good looks like, we said everything above four months in median progression-free survival and everything above 14 months in median overall survival would constitute a very good result. Looking at the both the all patient and in particular PD-L1 positive patient population, we are extremely encouraged by these results. We also showed the spider plots here, and here we've divided between non-responders and responders. Importantly, even for the group who are by the Response criteria, termed non-responders, we do see a very long and durable stabilized situation, which for many patients is also a significant clinical benefit. Of course, these long, stable situations for the non-responders also contribute significantly to the overall survival data that we're seeing.
The Kaplan-Meier for the overall survival, we've been through the data here, so this is just to put a little bit more nuance on it as you are looking at the split between PD-L1 positive, PD-L1 negative on the right side of this graph here. Already did mention that for the PD-L1 positive, we've not reached the median overall survival. For the PD-L1 negative group, we're looking at 7.3 months. I just want to emphasize this does also constitute interesting results for that particular patient population who do not have any other viable treatment alternative right now that is safe to provide. We will be focusing on the PD-L1 positive patient population, but we will not entirely forget the PD-L1 negative.
We will be assessing various ways to also be providing opportunities for those in the future development program. Very importantly, when you report clinical data for vaccine compounds, it's always imperative, we feel, to be able to show a correlation between the immune response that your vaccine induced at the clinical outcome. We see too many vaccine results out there that do not show this correlation. It's comforting to us to again be able to see a strong correlation between the antigen-specific immune response created by our vaccine and the resulting clinical outcome for the patients. This is one of the key parameters that also encourages our partners when we show the results to them.
Again here, just to put this data in context, we are focusing on the PD-L1 positive patient population since this is the patient population we are gonna prioritizing in the next step of our development program. On the left, we show you the data for VB10.16 + atezolizumab in the PD-L1 positive group, which is a group of 24 patients out of this trial here. Overall response rate, 29%. Median progression-free survival, 6.3. Very impressively, median overall survival not reached in this patient population yet. Comparing to what you would expect or what you see in a PD-L1 positive subpopulation with pembrolizumab and cemiplimab of 2.1-3-month progression-free survival and 11-13.9-month overall survival.
On the right, we show the data for Tivdak, which amounted to a median progression-free survival of 4.2 months and median overall survival of 12.1 months. We do deem these data for VB10.16 plus atezolizumab to be very competitive and indicate a strong clinical and very durable clinical response. We have done one additional subpopulation analysis, and that's the group of patients that we call PD-L1 positive patients who have received only one prior line of systemic anticancer treatment. The reason why we focus on this patient population also is because in VB-C-04 trial that we'll be starting towards the end of the year, which will be a potential registrational trial, we will be enrolling patients that are PD-L1 positive and have only received one prior line of treatment.
Although it's not exactly the same patient population because it's not the same prior line of treatment, it does indicate that the earlier you go in this disease stage here, the stronger the data becomes. Here we have impressive overall response rate of 40%. A disease control rate of 80%, that means four out of five women in this patient population actually received a clinical benefit. Median duration of response 17.1 months. Median progression-free survival, mind-boggling 16.9 months. Median overall survival not reached, so indicating more than 25 months at this point. These slides shows our development program. I wanna draw your attention to CO 3 and CO 4.
VB-C-04 is our potential registrational trial, the next step in the advanced cervical cancer patient population. It will be enrolling patients who are refractory to first-line treatment, which consists of a checkpoint inhibitor chemotherapy ± bevacizumab in the U.S. We will be running this trial in collaboration with the GOG, which is the clinical key opinion leaders and experts you want to be running this trial with in the U.S. We aim to enroll the first patient in the fourth quarter of 2023. This potentially could be a fast path to the market and the patients for VB10.16. In addition to that, we announced we are expanding into head and neck, also an important patient population with a significant unmet need. The first step in that direction will be VB-C-03.
We'll be testing VB10.16 in combination with pembrolizumab, which is applied by MSD. We have submitted the clinical trial applications for that program, waiting for the final go. We plan to be enrolling the first patient here in the first half of 2023. I will not bore you with repeating all these data, but just conclude in the end that together we find these data really indicate a potentially differentiating long-lasting antitumor response of VB10.16 in combination with atezolizumab, in particular in the PD-L1 positive patient group. 2023 have really been the year of VB10.16 so far. It will continue to be that.
As I said, we are now all hands on deck, with the initiation of the CO three trial, which is the first important step into head and neck, and the CO four, which is the very important next step into cervical cancer. Obviously the organization is highly focused on these two programs at the moment. With those words, I'm gonna hand over to our CFO, Harald Gurvin, to take us through the financials that we reported this morning. Harald?
Thank you, Michael. Nykode is well, financially well-positioned to grow and execute the company's strategy over the next years with a cash position of NOK 106 million at quarter end. We are also very pleased with the publication of our first ESG report in connection with the annual report for 2022. ESG is the key focus area in Nykode, and we continue to expand our ESG reporting going forward. As previously stated, we continue to explore and prepare for a potential listing on the Nasdaq Global Market in the U.S. We can unfortunately not give any guidance on timing, which will depend on, amongst other, market conditions. Looking at the income statement, we report the revenues of NOK 3.1 million in the first quarter relating to the R&D activities under the agreements with Genentech and Regeneron.
Our other income represents government grants from SkatteFUNN and the Research Council of Norway, where we have a total of three projects running. Looking at employee benefit expenses and other operating expenses, we have been ramping up the organization and our research and development activities over the last years, resulting in increased expenses. Please note that the first quarter of 2022 includes a non-cash reduction of $4.8 million in employee benefit expenses relating to Social Security cost accrual on share-based payments. In line with the increased interest rate levels, finance income has increased, mainly due to increased interest income. Overall, we recorded a net loss of $10.4 million for the first quarter of 2023. Moving on to the balance sheet. We have a strong cash position, as mentioned, of $186 million at quarter end.
Trade receivables were down in the quarter due to receipt of the NOK 2.5 million milestone under the Genentech agreement in the first quarter, while other receivables increased due to accrued interest and prepayments during the quarter. Moving on to equity and liabilities. We had total equity of NOK 148 million at quarter end, which represents a strong equity ratio of 72%. With that, I will give the word back to Michael.
Thank you very much, Harald. Before we open up for questions, we'll just take a quick look at the outlook for the next 12 months. Trying not to repeat myself too much here.
After the final results of VB10.16 VB-C-02 trial, which again, we feel was really transformative for the company and the program itself, we are very much focusing on getting the VB-C-03 trial, first step into head and neck, underway, and enrolled in the first half, as well as getting the all-important potential registrational trial VB-C-04 kicked off in the fourth quarter of this year. Also importantly, this morning in our report, we have announced that we will be disclosing the identity of the first or the next program that we're starting in the fourth quarter of 2023. That's the that will be the result of our internal discovery engine in the oncology fields, when we nominate the development candidate from that program.
Just keep in mind here that we have previously said we are running intensive discovery activities here, obviously looking at many different opportunities at the same time. What we'll be doing here is informing the market on which candidate and which indication we'll be focusing on for the next oncology development program. We'll also be providing updated survival data from the VB-C-02 trial in the first quarter 2024, and we're looking forward to be providing updates from our autoimmune program in the third quarter of 2023. With those words, I think we can open up for questions.
Thank you. We'll now be conducting a question and answer session. As a reminder, you may ask a question at any time by typing it into the Ask a Question feature on your screen. One moment please while we poll for questions. Our first question is, The New York Times yesterday published an article about BioNTech's mRNA personalized vaccine for pancreatic cancer, where it was stated a cost of production of U.S. dollars, I believe it says $100,000 per dose or $100 per dose. I'm not sure what that says. I'm sorry. Could you give us some color on how does this number compare to the production cost of your DNA vaccine, specifically for VB10.NEO?
Yeah, thank you very much for that question, Gonzalo, equity analyst from ABG Sundal Collier. I think I'm gonna hand over the work to Agnete to take us through a couple of perspectives on that one.
Yeah. It's a good point, Gonzalo Artiach. We saw the same numbers and I think we've mentioned before that manufacturing of a DNA plasmid is inherently a shorter process, meaning less labor work and also less steps. Because when you are manufacturing an mRNA-based vaccine, you first make the plasmid DNA vaccine as a template for then the mRNA, and then it's also formulated in this lipid nanoparticles. It's interesting to see the cost of goods numbers. I think that's where we can say that we believe cost of goods obviously will be super important in order to have a viable product that goes to the market, and particularly in early stages and in combination with a checkpoint inhibitor.
We do believe that the cost of goods will be an essential parameter in order to reach the market. Without mentioning anything about the comparison here, I think just looking at the manufacturing process, we believe this should be a differentiating factor between DNA vaccines and mRNA-based vaccines before reaching the market. I don't know if you want to add something, Michael.
No, I think that's perfect. I think you clarified it actually did say $100,000 per patient.
Thank you. Our next question is coming from Geir Håland from DNB Markets. As far as we understand regarding the nomination of an additional oncology development candidate for a new internal oncology program in the fourth quarter of 2023, this may be either a candidate with the potential to address multiple indications comparable to VB ten dot sixteen or more like a mono indication candidate. Could you please elaborate on the company strategy in deciding between these two paths?
Certainly. Thank you very much, Geir. Good opportunity to maybe give a little bit more flavor on how we work in the discovery engine of Nykode's. Imagine that we at all time have multiple programs running, and trying to find the best vaccine candidates against the various disease models. When we say we'll be coming out with a with announcement on which program to take forward, it actually means that we will be making a prioritization between the various different cancer types and the vaccine candidates within those cancer programs. When we do that, we are looking at various different parameters. One very obvious one is the unmet need that we're looking at for that cancer indication. That's, that's a factor which in itself is contributed by several different factors.
What else do you see in that development program, both on the market in terms of alternative treatments, and in terms of the competition that is heading through discovery and development, and how significant is the unmet need from the patient's perspective? That's one parameter we are looking at. The other one is the likelihood of success. And that of course will be, to a large extent, an estimate from our side. We are certainly looking at how effective in the preclinical model does our lead candidates seem to be. What kind of immune response can we induce? What kind of correlation between immune response and effect in the preclinical animal models are we looking at? That's a second parameter we'll be looking for.
The third parameter is a rough estimate on the development program and the associated costs that we look at in front of us. It is really a multi-parameter analysis that we're doing across the various programs before we decide which program to prioritize and which lead candidate within that program do we wanna take into preclinical development and then into development. It's a significant step for us because once we take that step, it is a little bit of... It's not fully irreversible, but that's where we really put our money and resources down on that candidate. From that point of view, we'll be starting on really building up and solidifying the manufacturing process for that candidate, and we'll be starting the final preclinical tox programs for that candidate.
For our vaccine, as we have said many times, we right now have a relatively easy tox program because there's a positive spillover effect between the programs. We still need to do a range of formal studies. It's important that we are very considerate before we take the decision on which lead program to, or lead candidate to bring into the development. We'll be going through the CMC upscaling process and the tox program before we start the first clinical program. It's very much a structured planning and execution process from that point on. I think we can take the next question, Kevin.
Thank you, Michael. We do have a follow-up from Geir Håland from DNB Markets. Assuming you'll combine the new candidate with a CPI and intend to finance the study yourself, is it an option to also pay for the CPI, or would you aim for some sort of partnership?
Yeah. Thank you very much.
Yeah, thanks.
You wanna add some color on that, Pia? Yeah.
Yeah, sorry. Yeah. Thanks, Geir. I mean, there's always an option to pay for a CPI. I think that always depends on the strategic consideration we take. Whether or not it will be in combination with the CPI is also dependent on the cancer indication, as well as the stage of disease that we will target in the end. That's not something we have guided on yet. You know that we are in very close collaboration with a number of CPI manufacturers. We do have obviously close collaborations with Roche and Regeneron as well as Merck. We will obviously take all those consideration into account.
The likelihoods of, pursuing a drug supply, for, with a checkpoint inhibitor is obviously high if we choose to go in an indication with a clinical trial design that, warrants a combination with a checkpoint inhibitor, I would say.
A follow-up question.
Next question, Kevin.
Sure. This is also from Geir as well. Being a highly innovative company, could you please elaborate on the priorities for the people in the R&D department at the moment?
Yeah. So we can add some color on that one. If we, you know, climb into the helicopter perspective, looking down at the research and the development departments, you would see an allocation of the people. The majority of people will be allocated to the VB10.16 program, which is still a wholly owned program, to the Genentech program, and to the Regeneron program. Those three programs take the majority of people we have in the R&D departments. If you dig or dive a little bit deeper down, you and go into the research and the CMC department, you will see additional resources being spent on our internal discovery programs, and that will be split amongst oncology, autoimmune disease, and infectious diseases.
I would guess right now with a slight overweight on the oncology programs. A fourth leg, which is also extremely important for us, is the continuous improvement of our technology platform. That's the efforts that, for example, led to the announcement of the fourth module at the AACR last year. It's important for us to emphasize that we continue to invest resources and capital in developing the next generations of our vaccines. As I said, majority of resources will be spent on VB10.16, the Genentech program, and the Regeneron programs.
Thank you. Our next question is coming from Gonzalo Artiach from ABG Sundal Collier . Regarding the announcement of the new vaccine by the end of the year, could you give us some color on what does the nomination of a lead candidate mean in terms of future development? i.e. How much preclinical work will be needed from that day in order to transition into clinical trials? How advanced are you at the current stage in terms of antigen selection and potential indications?
Yeah. Also a very good question. Thank you very much, Gonzalo. There's a couple of different perspectives on that answer. I think the first one to have in mind is, as long as we stay with a cancer vaccine or a Vaccibody that is in structure similar to VB10.16 and VB10.NEO, so that means it has the same targeting unit, the same dimerization unit, but it's just the antigens that will be exchanged. There is a high degree of spill, I mean positive spillover effect from the prior programs before entering the clinic. We've seen that multiple times that when we take a program into a new country, the fact that we have data from the other vaccines does bring a very high level of comfort already at the get-go.
Still, every time you bring something new into clinical development, there is a set of preclinical tox studies that will have to be done. I'm not calling it formality, but it has to be done to prove that it's safe to take it into the patient. If you compare it to other development or discovery programs, Gonzalo, the number of preclinical studies that we will have to do will be less as long as we stay with the already familiar vaccine structure that you are familiar with.
What will take, let's say what is on the critical path from the day we select our development candidate to we are ready to go into the clinic is actually the CMC related activities of being able to manufacture this on the GMP conditions in the right scale and secure the quality at every step of the manufacturing process, both of the substance and of the product. That is usually what is on our critical path, during that phase of development.
Thank you. We have a follow-up from Gonzalo. Regarding the COVID-19 candidates, you mentioned that you are open now for partnerships. How active are you planning to be in terms of looking for potential partners? What is the point of view of Adaptive regarding these decisions? Is there any plan to continue working together with them in other segments and indications?
I think that's a question for you, Agnete.
I think, thanks for the question, Gonzalo. I think we are always open for partnership and also always exploring partnerships because different kinds of partnerships can make sense in order to optimize the advancement of our candidates over time, for pushing them forward to the market with the highest likelihood of success. That's also the consideration we now have for the COVID candidates at this time point, the optimal way forward for the COVID vaccines in the current landscape, current regulatory landscape, current approvals that we've seen, et cetera. There are certain considerations that we take into account and wanna employ the resources in the optimal way.
Now it's really a partnership path that we believe would be the most sensible in order to pursue an opportunity that VB 102210 or other candidates that we have could reach the market in the optimal manner. We do have some activities ongoing in order to look into the potential opportunities with, and I think we have all the same common wishes and background for making those kind of decisions. We do really appreciate the collaboration we have with Adaptive on this candidate and their epitope selection capabilities. We'll guide on future potential collaborations with Adaptive and/or other partners when these become relevant.
Thank you. A follow-up from-
Thanks.
From, Gonzalo. There's been a lot of talks regarding the FDA getting more and more hesitant to approve drugs based on single-arm trials. This seems to be an even more material trend now. Given the fact that the FDA issued a new draft guidance with special mention on that matter, could you please give us, sorry. Could you give us some color on how you see this moving forward? How much can this compromise... I do apologize. How much could this compromise your potentially registrational trial?
Yeah. Good, good point also to bring up in this discussion here, Gonzalo. Here I wanna emphasize or repeat what I've said earlier on this topic also. The guidance and the also the updated guideline that FDA issued is in no way new to the industry. I think it's very much in line with what both FDA and all other relevant stakeholders have been saying for years, that we need to toughen up a little bit on the, I would almost call it misuse that we've seen of on these regulatory tools in the U.S. that people get accelerated approval without actually committing to the confirmatory trial. That's also why they've made it slightly more difficult and they have strengthened the wording around when can you use what kind of trials.
Very important to note, they have not excluded single-arm trials, but they are saying it needs to be justified. We are in dialogue, I think we've said that repeatedly, with the authorities in the U.S., and we can't say anything about the nature of those dialogues at the moment except that they are progressing. Those dialogues will lead to the final conclusion on how exactly we want to design VB-C-04, the VB-C-04 trial. We feel confident there is a path forward for the VB-C-04 trial. Exactly how we decide to design it in the end, we still have to await the final outcome of the discussions with FDA before we can tell you that.
e we're we're guiding that we will be starting the trial in in the fourth quarter this year-You can you can assume that it's not gonna be too far out in the distance when we are ready to tell you basically the conclusions of of our deliberations with with with the FDA. So in conclusion, you know, right now we feel confident that we'll be able to reach a good conclusion with the FDA on how to design this trial here and and bring the VB-C-04 trial forward as a potential fast track to to the market. That that that's our strong assessment right now.
Thank you. Our next question is coming from Arvid Näsander from Carnegie. While the 2 LCC could offer a fast path to market, the addressable population is fairly small. Considering its disappointing results with Roche's BioNTech's mRNA vaccine in the advanced pre-treated setting and Moderna's promising results in the adjuvant setting.
Mm-hmm.
What makes you sure the advanced pre-treated setting is the right potential to pursue? How did you balance the risk reward when arriving at the strategy?
I think also here, Arvid, and thanks very much for bringing up this important aspect also. That's a good opportunity for us to clarify a couple of positions here. We do not think advanced cervical cancer is the only right area to go into. We very much agree that adjuvant setting is also a very interesting area to take our vaccines, not only VB10.16 into. For us, it's more a matter of prioritizing the sequence of order of which we take these steps. We've said that taking the...
On the back of the very, very positive VB-C-02 data in advanced cervical cancer, we've said that taking VB10.16 into the VB-C-04, so staying in the advanced cervical cancer field and designing the trial that the way we intend to trial it will constitute a potential fast path to market, which we think is extremely important, not just for these patients, and not just for VB10.16. To show that we can actually come forward with the market, but also for Nykode Therapeutics as such, because that will be a true test of the potential of the ability to bring products to the market. Now, you're right. We also need to consider how we advance the addressable market patient population of VB10.16.
We have already disclosed that we will be opening up for head and neck and advanced cervical cancer. I think we have hinted that on the back of the trial.
Michael, you were gone for a while.
I'm hearing you both speaking at the same time. Sorry.
I did not hear Michael for a long period.
He was there. I'm sorry. Michael, please-
Very good. I'll just continue. Yeah. Just wanted to give you the follow-up coming from Arvid. Just give me one moment, please. With Seagen guiding for top-line results from-
Kevin.
Can you hear me?
Kevin, can I interrupt you?
Yes, please.
I hear the. I see a message that we've gone off sound. I just wanna.
Nope, I hear everything is totally clear.
Very good. Yeah, very good. Excellent.
I hear you.
Good. Yeah, I'll just finalize that one there, Kevin, the question to that one there. We just want to repeat the guiding we also gave when we reported the positive results for VB-C-02 that we indeed look at adjuvant setting as a very relevant patient population to also be taking our VB10.16 in, both in advanced. Sorry, both in the cervical cancer field, but also in the head and neck. We just need to get our heads around the planning for that one. Thank you very much for that question, Arvid.
The follow-up from Arvid. With Seagen guiding for top line results from Padcev's confirmatory trial around year-end 2023, what makes you confident that an accelerated pathway will still be available by the time VB-C-04 is top-lined?
Yeah, here, sorry, Arvid. Here we have to be a little bit careful or sensitive on what we. We obviously have a lot of discussions ongoing with the stakeholders in the field. You'll have to wait a little bit on our updates on the program, the way we decide to get, I think, the full flavor on that one there. Our, the conclusions we've had for, based on discussions both with the FDA and with the clinicians, in the U.S. tells us that the path is open in front of us.
I'm not really sure we are ending up at the same conclusion that you're ending up here, that around the Padcev trial. We remain quite confident in the path going forward, also in the window of opportunity, regarding the follow pool here.
A follow-up from Arvid Necander from Carnegie. Considering the commercial opportunity in 2L r/mCC and investments needed to build a fully fledged commercial organization, it seems like it would make sense to partner VB10.16. Could you give us an update on your go-to market strategy and potential timelines for partnering?
Anne, I hope we have you on here. You wanna add some color on that perspective?
Yes. I think we've said several times that we are continuing to build the company and, at this point in time, we have the capabilities and think it's a wise decision for us to pursue late stage clinical development of our candidates. That VB10.16 is running rapidly forward and that we do not have the intention to build up a commercialization and marketing department for, to be ready for VB10.16. Yes, we will be looking for a partner for VB10.16.
Okay.
At a certain time point. That's true. Exactly when and where is something that we are continuously evaluating. These data are also affecting our decisions and that's something that we will take into consideration in order to make the optimal plan for the success of VB10.16 and for the value for everyone on this asset.
Our next question is coming from Rohan and Sebastian from Van Lanschot Kempen. Congrats on all the progress. Some questions from our side. You briefly mentioned the interim results of the VB-N-01 trial. Can you provide some color on the timelines regarding updated results of VB-N-01, VB-N-02 regarding... Regarding VB, would you like me to stop there or keep going?
Yeah. Yeah, no. Yeah, let's take this one first.
Please.
Thank you very much, Sebastian. Unfortunate, as we said a couple of times before, the communication strategy for VB-N-02, sorry, VB-N-01 and VB-N-02, so VB10.NEO in general, is really on the shoulders of our partners from Genentech. We are from time to time in discussions with them on what can be disclosed and what cannot be disclosed. As you can see, they are forthcoming and supportive trying to allow us to disclose or release data from time to time. We just released a small batch of immunogenicity data from the VB10.16 VB-N-01 trial that Arnout reviewed earlier today.
Unfortunately, we cannot give further guidance on the release of either of those two trials. We really have to await our partner's decision to release on that one.
The second part to their question is regarding VB10.16, you mentioned that you mainly focus on PD-L1 positive patients. Can you please describe how you see its path to market? Is there accelerated approval potential?
Yes. I think that's why we really emphasize the potential of the VB-C-04 trial. The VB-C-04 trial will be enrolling PD-L1 positive patients with advanced cervical cancer who are refractory to the first-line treatment in the U.S., which is the pembrolizumab + chemotherapy + chemotherapy ± bevacizumab. That's a patient population that currently do not have any good, safe, other alternative treatment approved in the U.S. That will be a potential registrational trial, and we do see that as a potential fast path to the market in the U.S. From there, we will, of course, be expanding the scope of VB10.16, as we have indicated, into head and neck, where we currently are not seeing exactly the same opportunities in terms of a fast path.
There we're actually starting in first-line treatment, and we'll also be looking at bringing our program into the adjuvant setting in the future, both in cervical cancer and head and neck. We've said repeatedly that we will not be forgetting the PD-L1 negative patients, and we will not be forgetting the additional cancer types that are driven by HPV-16.
I'll follow up as well. Can you provide some color on the intended patient population for VB-C-04? How many patients? Will all patients be PD-L1 positive? Will all patients have prior CPI exposure?
Yes. I think I effectively answered that question right now. We will be enrolling patients who have failed first line, which includes pembro in the U.S. By implication, therefore, the patients will be PD-L1 positive. This is something, of course, we will be checking upon enrollment also. That's a yes to both of those questions, Sebastian.
Thank you. Further follow-up. On your autoimmune pipeline, what can we expect timing-wise for an update regarding progress or possible disclosure of targets?
Arnout, do you feel like adding a bit of color on that one?
Yeah. The autoimmune program that we have shown you and then the data that we've shown you from this program before, the focus initially is really to develop the optimal platform technology that we can pursue for autoimmune indications in the future. We are currently focusing a lot on identifying how and where we should utilize the platform, which targeting units, which potential fourth modules, et cetera, that will be the optimal one in order to make sure that we can really skew the immune response into the intolerance across different future potential autoantigens.
That's something we are doing in parallel with pursuing and reviewing the different indications and potential clinical programs that would be the most relevant ones that we would like to pursue when we decide on the optimal lead candidates. Which is basically what Michael also explained in detail when it comes to our oncology programs. There's a lot of preclinical data where we nail down the design of the vaccines before we go and nominate a lead candidate.
With the autoimmune program, I think it's very important for us that this is a novel technology, a novel technology platform where we get a lot of feedback on the positive potential of this platform being able to induce a very specific, antigen-specific tolerance. Still early stage, I would say. An update will be an update, and then we'll see also on. I think we will provide at least, give you, quite a lot of indications of where we would like to go with this program.
Thank you. We've reached the end of our question and answer session. I'd like to turn the floor back over for any further or closing comments.
Yeah. Thank you very much, Kevin, and thank you very much to all of you for the breadth and wealth of questions here. It's always a little bit more fun when we have engagement through these questions. We appreciate that very much. Thanks to everybody else for listening in to this first Q report.
Thank you. That does conclude today's teleconference and webcast. You may disconnect your line at this time and have a wonderful day. We thank you for your participation today.