On exploring our unique proprietary immunotherapy platform, which uniquely targets the antigens to the antigen-presenting cells, and in turn generates a strong CD8 killer T cell response, which it has been shown to be correlated with clinical responses in solid tumors. Our technology is modular in its build-up, which also provides a high degree of versatility that allows us to easily incorporate new antigens and adapt the products to new diseases across the oncology, infectious diseases and autoimmune space. We are dedicated to advancing our wholly owned and lead assets, VB10.16 and immunotherapy, developed for HPV 16 driven cancer types. We are very happy to have been reporting both positive clinical data from that program back in May, and followed up with additional positive data in November last year.
We are very much looking forward to be reporting the final data from the VB-C-02 trial in the first half of 2023. We've also announced an expanded development program, an ambitious one at that, which includes a potential registrational study in advanced cervical cancer to be initiated towards the later part of 2023, as well as an expansion into head and neck with a dose escalation study that we'll be doing in combination with Keytruda to be initiated in the first half of 2023. We believe in partnerships and have been signing a number of transformative partnerships for the company, including two large out licensing deals with Genentech and Regeneron, as well as other partnerships with top tier partners.
We're well capitalized with a cash position of $26 million as per December 31st, and we'll come into further details on the financial reporting towards the end of this call. Both fourth quarter and 2022, its entirety has been a transformative year for Nykode. We've been announcing a string of positive results across our programs, including our wholly owned and lead asset, VB10.16, as well as our individualized cancer vaccine, VB10.NEO, which we develop in combination with Genentech. We've also announced a collaboration with MSD on the combination of VB10.16 with Keytruda in the VB-C-03 trial.
We'll tell you more about this trial in a few minutes, as well as a strategic manufacturing partnership with Richter-Helm BioLogics that will give us certain securities on supply chain flexibility. We are, as I mentioned, also very much looking forward to the major event, which is the final reporting from the VB10.16-C-02 trial, which has been enrolling patients with advanced cervical cancer. This final analysis will cover the entire treatment phase for all the patients in this trial here. We've also, post the Q4, announced a collaboration with GOG Foundation, which will help us both design the optimal C-04 trial and also help the execution of the C-04 trial. We'll tell you more about that in a few slides.
With those words, I'm going to hand over to [Agnete] to take us through the key highlights from the positive data we reported in fourth quarter.
Thank you, Michael. We will start off with some focus on the individualized cancer neoantigen-based vaccine program that we are currently running then in tight collaboration with Genentech. This is where we work with the individualized neoantigen specific vaccines. These are custom designed and manufactured as one vaccine per patient, really based on mapping each patient's cancer specific mutations. If you have followed the field recently, there's been multiple positive data, and Moderna and Merck announced at the end of last year interesting clinical benefit for their individualized neoantigen specific cancer vaccine. This was in an adjuvant setting, but we really see that this has generated new enthusiasm for the promise of cancer vaccines, particularly than in early stage disease.
It's important for us to highlight that Nykode is a key player in this field. We were one of the first companies in the clinic with an individualized cancer vaccine, and that's our VB N-01 trial, where we had the first patient, first dose already in 2018. Nykode has also last year, after entering a partnership with Genentech in 2020, we were presenting positive data in multiple indications. This is then in the trial setting with checkpoint inhibitor experience and advanced metastatic setting in multiple different indications. It's a bit different setting from the data that we've seen from Moderna and Merck. We presented updated positive immunogenicity data from this trial, which shows us and confirm this broad and strong CD8 skewed immune response.
You've seen before that in preclinical studies, we are able to show a broader and stronger and more CD8 skewed immune response than multiple other vaccine technologies that focus on the antigen alone when we incorporate our targeted, APC targeted technology. We also said that we have 100% manufacturing success rates with this. Important bit, this is on the DNA plasmid backbone, and is also safe and well tolerated across the studies we reported so far. Briefly, VB N-01 is the study where we reported this positive data. This is the trial that we initiated before entering the partnership with Roche Genentech. After signing the agreement with Roche Genentech, we started at the end of 2021, the N-02 study, which is ongoing then in more than 10 indications.
This is where we're doing also a dose escalation. Recently, we have also revealed that we are increasing the dose up to 9 mg in this trial, which will be the first trial where we look first, obviously, into safety over a three-time higher dose than what we tested before. Subsequently, if this is safe, we will be able to investigate whether we have even further increased efficacy by increasing the dose. This trial is really just to highlighting this data that we presented in the fourth quarter. Based on what we've seen here, the breadth of the response is really confirming what we've seen in preclinical studies. We generate a response to a high number of neo-epitopes also across, in this case, all patients.
We see a neoantigen-specific response after predicting and selecting epitopes based on each patient's tumor and manufacturing one vaccine per patient. We also see that these are primarily de novo responses, which is important that they are new to the patients after starting vaccination, but also have the inability to amplify these responses that were already preexisting in the patients. Importantly, we continue to see this strong CD8 dominated T cell responses in this trial. These data are not just important for us for the individualized cancer vaccine program, but it's really giving us comfort on the translatability of our vaccine platform's unique abilities compared to other vaccine technologies that goes across the platform and not just per product.
For VB10.16, this is our wholly owned asset, and you've seen in 2022 throughout that we are focusing on rapidly advancing this asset now in multiple different indications. It has the potential to treat patients with an HPV 16 positive cancer across both cervical head and neck and other diseases that are caused by HPV. We have a pretty broad program ongoing with VB10.16. Importantly here, we are now very much looking forward to report final data from the VB-C-02 trial in cervical cancer. We reported interim data from that trial back in May last year.
Now we are getting ready to do the final analysis and then report the data about how these patients will do after a whole year of treatment or more. Based on the interim data, we have also decided to expand into head and neck and cervical cancer, as well as other potential trials. I'll go a bit more into the rationale for this in the subsequent slides. Importantly here, as a reminder, for the interim data that we announced last year, in anticipation of the future updated data set that will come out for VB-C-02. Remembering that this trial was in heavily pretreated advanced cervical cancer patients. We have said before it's full enrolled, so 52 patients.
This was then treated with a 3 mg dose of VB10.16. We have highlighted that this patient population includes a high number of patients with multiple prior systemic treatment lines, so they have failed multiple lines of systemic cancer treatments. As well as we have also a quite high percentage of PD-L1 negative patients, knowing that these patient populations with later stage as well as PD-L1 negatives are in general the patient populations that respond less optimal to checkpoint inhibitors. The last interim analysis was a preset where we had 18 patients that had reached the 18-week scan, as you can see here in the spider plot.
There were multiple patients that had been followed for a shorter period than 18 weeks, and only a few patients that had gone through the entire first year of treatment. This is really what we are then expecting to report within the next few months. All patients, all 52 patients would have had the possibility to be followed for the entire first treatment year, as well as some patients we will have longer term follow-up when it comes to overall survival and durability of responses.
We have highlighted before that these very long-lasting clinical responses that we see in those patients that were followed for a year last time is what we are most excited about looking into for the final data analysis to see if we can repeat that pattern in more patients. That will be very important and meaningful for the promise of VB10.16 in the future. We have also looked into previously, this includes PD-L1 positive as well as negative patients. We see a very high objective response rates in the PD-L1 positive, higher in PD-L1 positive than negative. Taking into account that the checkpoint inhibitor monotherapy in this indication has published around 14%-16% objective response rate in PD-L1 positive. In general 0% in PD-L1 negative patients.
It will be important for us to look into these subpopulations also in the subsequent readout. I think for the key inflection points that we are now seeing ahead of us for VB10.16 is this long-term follow-up from the VB-C-02 trial. Importantly, we will look into patients that have had a minimum of 12 months. It's PD-L1 positive as well as PD-L1 negative patients that we will see how response treatment, and it will be patients with both 1 or more prior systemic treatment lines based on the data that we've also released earlier that there is a higher likelihood of seeing strong responses in patients with one or two prior systemic treatment lines than those that have failed more than three prior systemic treatment lines.
This will be both an update on our objective response rate and disease control rate. Importantly, also, new parameters that we haven't looked into before, will be duration of response and overall survival. For the C-O2 trial, that's actually a trial that we are expecting to have the first patient first dose also in the first half of this year. In addition to the dose escalation trial that we have mentioned for the N-O2 trial, this is also a trial where we will be able to look into how then a higher 9 mg dose will perform in comparison with the 3 mg dose.
It will be in PD-L1 positive patients, where we've seen also in VB-C-02 trial that we have the highest efficacy, and it will be in first line patients, where we also have seen before that we have the highest efficacy. We will be in combination with pembrolizumab after we announce that we sign a collaboration supply agreement with Merck in December last year. For VB10.16, in addition, we have an important program ongoing and with preparing for the first patient, first dose also in the VB-C-04 trial, which is a potential registrational trial. This is a trial that we now recently announced that we will do in tight collaboration with GOG. It is to be initiated in Q4. We are currently on track to do that.
It will be then also in recurrent or metastatic cervical cancer setting. These will be refractory to first line treatment, then including the checkpoint inhibitors performed in U.S. This is really a patient population with a high unmet medical need, where we have a potential for fast to market. VB10.16 will then be given in combination with a selected checkpoint inhibitor that we will inform you on the decision on which one before we start the trial. As mentioned, we are extremely fortunate to have been able to attract the collaboration with the Gynecologic Oncology Group Foundation. This is a U.S.-based expert group that is really focused on gynecologic cancers, and it has a 50-year history of designing and executing clinical trials in cervical cancer.
n involved in most of the treatments that have had approval in these gynecologic settings. The last from the operational point of view is importantly our strategic partnership with Richter-Helm. As Michael mentioned, this is something that's important for us to secure and optimize the manufacturing moving forward as a company with multiple programs running in parallel. This is a highly reputable plasmid DNA manufacturer with a proven track record. This will give us highly comparable cost of goods and maybe most important, a flexible forecasting model and that will secure capacity for our entire portfolio, both with our own programs, but also then for delivery to our partner programs
The ability for us to do a potential tech transfer to partners is also something that will be supported by Richter-Helm. That includes our own Nykode IP. This has been an important collaboration for us moving forward. Get my time back.
Thank you very much, Agnete. Just a few words on the organization, which as you will see on the next slide, will continue to grow. Although if you compare the last quarterly report, you'll see a slightly lower, some would say more controlled pace. We now reach 157 employees across the organization, which includes all people who have signed and started working for the company. The distribution across the different functions is on a stable path or trajectory with 50% engaged in research and approximately 4% engaged in development activities, including CMC. And with those words, I'm gonna hand over to Harald Gurvin, our CFO, for a review of financial numbers.
Thank you, Michael. Nykode is financially well-positioned to grow and execute the company's strategies over the next years with a strong cash position of $206 million at the year-end. We're also very pleased with the successful uplift to the main list of the Oslo Stock Exchange in the second quarter last year and the subsequent inclusion in the Oslo Børs Benchmark Index and Oslo Børs Mutual Fund Index in the third quarter. As previously stated, we continue to explore a potential listing on the Nasdaq Global Market in the U.S. We can unfortunately still not give any guidance on timing, which will depend amongst others, on market conditions.
Looking at the income statement, we report the revenues of $2.7 million in the fourth quarter and $7.2 million for the full year relating to the R&D activities under the agreements with Genentech and Regeneron. This is down from $31 million and $33 million, respectively, for the same period in 2020 due to a $30 million upfront payment booked under the Regeneron agreement in the fourth quarter of 2021. Our other income represents government grants from SkatteFUNN and the Research Council of Norway, where we had a total of four projects running in 2022. Looking at employee benefit expenses and other operating expenses, we have been ramping up both the organization and our research and development activities over the last years, resulting in increased expenses.
Overall, we recorded a net loss of NOK 12.2 million for the fourth quarter and NOK 42.7 million for the full year 2022.
Change that.
Moving on to the balance sheet, we have, as I said, a strong cash position of NOK 206 million at year-end. Looking at the trade receivables, these are the amounts invoiced under the Genentech and Regeneron agreements. The reduction in trade receivables is due to a NOK 20 million milestone from Genentech, which was invoiced in the fourth quarter of 2021 and received in the first quarter of 2022. Lastly, moving on to the equity and liabilities, we have total equity of NOK 157 million, which represents a strong equity ratio of 71%. With that, I will give it back to Michael.
Thank you very much, Harald. Just to finish off reviewing our achievements for 2022, it was a both busy and successful year with a lot of progress across our programs with the positive results from our VB10.16 VB-C-02 trial in vast cervical cancer, as well as the announcement of the next studies for VB10.16 in cervical cancer and head and neck cancer. We also reported positive results from our T cell focused candidate in our COVID program. We reported positive immunotherapy results from our individualized cancer vaccine that we are developing together with Genentech. We reported the announced the strategic manufacturing collaboration with Richter-Helm. Looking ahead is also going to be a busy and hopefully as successful year in 2023.
Most importantly, obviously, we are looking forward to be able to announce the final analysis data from our VB10.16 VB-C-02 trial, which will take place in the first half of 2023. We also look forward to announce the initiation of our expansion into head and neck with the VB-C-03 trial, the trial that we are running together with MSD, will provide Keytruda for the combination. We're looking forward to get the potential registrational trial VB-C-04 off the ground, hopefully initiating that towards the end of the year. This is the trial we are running in collaboration with U.S.-based GOG Foundation. We are very much looking forward to be able to update you with additional preclinical data from our autoimmune program in the third quarter of 2023.
With those words, I'm gonna hand back to operator and open up for questions.
Thank you. To the audience, just a reminder, you can submit your questions by typing them in the ask a question field on your screen. Our first three questions come from Gonzalo Artiach with ABG Sundal Collier. The first question, recently, Moderna and Merck obtained Breakthrough Therapy designation for mRNA-4157 melanoma vaccine based on their phase IIb trial data. Could you also apply to the FDA for Breakthrough Therapy designation for VB10.16? Could the fact that VB-C-02 trial was run only in Europe and not in the U.S. affect the outcome of the potential decision of the FDA?
Thank you very much, Gonzalo, for that excellent question. I'm gonna break the answer into two different sets. To the first question, could we in theory apply for Breakthrough designation for VB10.16? Yes, we could. Due to the requirements for Breakthrough designation, we believe the correct timing for such an application would be when we have the interim results from the C-04 trial that we will initiate towards the end of the year. In that sense, the location of C-02 in Europe is not in any way a hindrance for a later Breakthrough designation.
Thank you. A second question regarding the GOG Foundation collaboration. Could you give us some color on what are the steps and key requirements that the GOG Foundation needs or demands in order for them to join a trial such as C-04 as collaborator?
Yes, of course, this is a question that should be better directed to them, but I'll give you our flavor for what we believe they consider important and why they choose to enter a collaboration with us. I think first of all, they need to be excited by the technology and the product candidate that you're entering into a collaboration with them around. We've had long discussions and interactions with the GOG on the platform technology of Nykode and in particular VB10.16 and the interim clinical data that we have shown earlier for this program. I think that's the most important starting point for a fruitful discussion with GOG. They need to have some confidence in the company that they wanna work with.
Finally, they need to believe in the both the trial design and the subsequent development strategy that you put forward. That's why it's been so important for us to discuss the development strategy and the potential registrational nature of C-04 and a potential path to market path for the product candidate. It is as you can hear, a multifactorial element when they consider who they wanna work with. Next question.
Thank you. Based on your VB-C-02 interim data, you reported that patients that receive VB10.16 in the 2L or 3L of treatment seem to have a better response to the vaccine, higher efficacy numbers, reaching an ORR of 30% in average combining these two lines. Does this have any implication in terms of future patient selection in your upcoming VB-C-04 trial?
Yeah, good question. I mean, I think we said before that there are no surprises to us that you are expecting a higher efficacy in the earlier lines of treatment than in the later line. This is one of the reasons that in the VB-C-02 trial, where we are not really controlling how many lines the patients have received before, we were a bit concerned seeing the number of patients that came in with the later lines of treatment. Looking into the efficacy numbers, we also confirmed that in the earlier settings, we see a higher objective response rate as well as disease control rate. It's not a surprise to us.
I think yes, you see it both in the VB-C-04 trial as well in the VB-C-03 trial. In the VB-C-03 trial in head and neck, we're doing it in first line patients and in the VB-C-04 trial, in patients that have then failed one prior line of treatment, which will be then including the checkpoint inhibitor treatment in the first line. Yes, expected, and I think you can see that in our future development plans that we're moving in that direction. These are also PD-L1 positive patients in both of those trials, which is also another parameter we're looking to patient selection that has the highest opportunity to respond to treatment. Next question.
Thank you. We have three questions from equity analyst Geir Holom with DNB Markets. You recently stated that you will be spending most of your resources, both capital and manpower, on oncology, second on autoimmune diseases, and last infectious diseases. One, has your experience from the SARS-CoV trial strengthened your view on Nykode's potential within infectious diseases? Two, we know you believe a balanced T cell and B cell response is an interesting way forward with infectious diseases. Do you think the current construct of the Vaccibody molecule, and especially the targeting unit, produces sufficient B-cell response to achieve that balance? Three, could you elaborate on how you are currently working on your preclinical efforts within autoimmune diseases, i.e., how much of your company's manpower is put on these efforts? Thank you.
I can take a stab at those. Yes, we have recently announced the data from the SARS-CoV-2 trial for our T cell focused candidate, and that gave us the confidence and strengthened our view of our technology's potential to generate also strong and broad T cell responses as well. Here we also see the CD8 skewing of the immune responses to in an infectious disease setting, and it's basically the same as what we've seen in the oncology setting. It's a platform feature that we are continuing to see across antigens, whether they are from infectious diseases or from oncology.
Importantly, that is with a particular targeting unit that we have chosen to work with, which is based on the T cell focused and cross presentation and CD8 skewing. This is something we see then also across into infectious diseases, which can be important in order to eliminate, for instance, virally infected cells. I think the safety that we also presented from this trial gives us the opportunity to work in a prophylactic setting, for instance as well. For the second question, I think we've seen before and we've published data on the platform, on the opportunity for us to work with this really modular technology.
We can work on fine-tuning our platform technology in order to skew it to more T cells or B cell responses, Th1, Th2, and a lot of details by only simply changing the targeting unit. Recently in 2022, we've added on this fourth module technology in addition that gives us another layer or two in order to further control the immune responses in different directions. When we move into different diseases, in infectious diseases, there may be different correlates of protection that may be an opportunity for us in the future to custom design a vaccine that gave us the right kind of immune response to that particular disease. That's the future opportunity working on the modularity and the targeting unit that we have in our vaccine.
That is really for the third question on autoimmunity, something that we are then employing also for autoimmune diseases. A bit similar to what we could do in infectious diseases, by changing the targeting unit and making sure it goes to certain subsets of antigen-presenting cells, that are more of the tolerogenic, DC, type, and also adding on these fourth and fifth modules in principle that can further make sure that this local immune response is skewed to immune tolerance, and regulatory T cells that will be antigen specific.
We believe that the technology as we have presented it is unique when it comes to how specific and how many different modules that we are employing in one vaccine technology in order to make sure it can lead to antigen specific immune tolerance compared to whatever else is out there in development for antigen specific autoimmunity. It's still early stage disease, early stage preclinical setting for us. In that case, we are obviously having a lot of focus on autoimmunity, and we have a strong belief that this can be extremely important for the company and generate a new leg for us. When Harald is looking at the finances, it's not taking a huge bulk of the finances.
It's taking more in our brains, I think at the moment.
Thank you.
Next question.
Our next question comes from Bertrand Delsuc with Biotellytics. Hello. What to expect from the 9 mg dose? How do you know how DCs are saturated or not in terms of antigen internalization and antigen presentation?
That's a good question, and we have a lot of data on this from preclinical settings and then generating more and more insight into these questions as we speak, both ourselves and with partners. We do see that we can, we do have a very strong dose response in preclinical settings where we can continue to increase the dose. It also is an effect on the number of injection sites. If you separate the dose, the higher doses in multiple injection sites, you avoid this potential saturation that you are potentially referring to here and can continue to increase the total systemic responses in the patients. We are also very much...
The first thing which we will be looking into is whether it's safe, and it's really because the 3 mg dose that we've seen in all the trials up until now has not presented itself with any concerning safety signals. That's the reason why we are moving into a higher dose. We want to really explore if there can be additional efficacy left on the table. The data that we will generate will answer whether we are at the top of the curve or whether there is more efficacy to be taken out by increasing the dose without sacrificing anything on safety. Next question.
Thank you. Just a reminder to the audience to submit questions, type them in the ask a question field on your screen. We have an additional question from Bertrand Delsuc with Biotellytics. Do you have plans for VB10.NEO in earlier setting than advanced and metastatic, like the neo-adjuvant one in melanoma or other cancer types?
Yeah. For VB10.NEO, we are obviously not in control of communication of the further development plans as this was out licensed to Genentech in the future. I can maybe comment on a general basis that, as mentioned before, the earlier we meet the patients with a vaccine, we believe that the likelihood of seeing efficacy will be more and more evident. Since our vaccine has the safety profile that we now referred to a few times, we believe also in the future that it has a place in early lines of treatment. However, we are quite enthusiastic by also seeing efficacy in advanced patients at this stage.
We believe that there is an opportunity along the treatment paradigm.
Thank you. There appears to be no additional questions at this time. I'll hand the floor back to our speakers at Nykode for closing remarks. Thank you.
Thank you very much. Once again, a big thanks to all the participants for joining for this update on our quarterly results and company highlights. We look forward very much to beginning bringing you further updates, in particular from the final analysis of the C-02 trial, which will be due in the first half of 2023. With those words, I think we can close the call today. Thank you very much.
Thank you. This concludes today's conference. All parties may disconnect. Have a good day.