Good afternoon, everybody. Thank you for taking the time to listen to our first quarter of 2022 presentation. As usual, I'm here with Jens, our Chief Medical Officer, and Hans, our Chief Financial Officer. We will go through the highlights of the quarter and after this session, we will be going through a Q&A part. Please send your questions if you have any while we present. But I also want to take the opportunity to thank all of the shareholders and interested parties that have been sending us a lot of questions, and we will try to address the majority of them when possible. Again, thanks everybody, and we can start. As you know, I need to show you this slide, but let's move to the presentation.
I will start with the highlights of the quarter. Jens will give a operational update, particularly on the clinical trials. Hans will cover the key financials, and then I will close before the Q&A with the expected news for the next 12 to 24 months. If we can move to the next slide. As in the past year, in 2021, we also had a very good first quarter in 2022. We strongly continue to progress towards key milestones. The INITIUM and the NIPU studies are on track, so we can expect the top line results during the first half of 2023 with good patient enrollment. We are very happy that we received a patent extension in the US, extending the commercial patent protection for UV1.
We had another patient that moved from a partial response to a complete response in the UV1-103 study and with now a complete response rate of 33%. We, after you know, 63.3 months, finally reached the median overall survival in the first Phase I study in melanoma where UV1 was combined with ipilimumab. We continue to present at medical scientific conferences very valuable data from the clinical development activities. We also continue good progress in the development of TET platform. In the next slide, I would like to just touch briefly on the update on the enrollment of the patients. Jens, of course, will cover this in more detail.
What we are pleased to see is that, despite the continuing challenges of the COVID pandemic to some centers in some countries, we have enrolled now 17 patients in this past quarter. We have now 137 patients in INITIUM out of the total of 154. In NIPU also continues to progress very nicely, 78 out of the 118 patients compared with 66 patients in the last quarter report. DOVACC, of course, started enrolling patients only in December of last year, but it is progressing and Jens will touch a little bit about some of the initial challenges for initiating clinical trials during this Phase.
FOCUS, as you know, a study running in head and neck, all in Germany, continues to enroll patients, 18 this quarter versus 10 the previous quarter. We are all excited too and expect during this quarter that the first patient will be enrolled in the LUNGVAC study, the non-small cell lung cancer study that will be running in Norway. As I mentioned, you know, it's not as visible as it was in the past, but several countries and several centers still have challenges with personnel. I think this is also reflected in some other industries, like for instance, the aviation industry. Where you don't see patients or the personnel getting sick, but they test positive and they need to be away from their places of work.
This has been impacted but, you know, we continue to be very happy with the enrollment of these patients in these studies despite these challenges. If we can move to the next slide. As I mentioned, we received a notice of allowance from the U.S. Patent Office on a patent application we did for our vaccine in combination with checkpoint inhibitors. This patent will cover cancer treatments that include UV1 in combination with anti-CTLA-4, anti-PD-1 or anti-PD-L1 antibody checkpoint inhibitors. This is very important because from a commercial perspective, this extends at least until June 2037 the protection in the U.S. for UV1 when using these combinations.
Of course, these timelines are before any patent extensions and data protection, as you know, is customary in biotech and in pharma. Of course, we have similar patents pending in other territories, and we will be informing you when these will be granted. In the next slide, we move now to the operational part, and I give the word to Jens.
Thank you, Carlos. Good afternoon. I will give a presentation of the clinical program we have in Ultimovacs. If you can move to the next slide, you can see here the three first Phase one trials that were conducted in Ultimovacs. You have seen this table several times before. What is new here now is that we have reached the median overall survival in the malignant melanoma trial. That was a trial in 12 patients where we combined the vaccine with the ipilimumab. Eight of the patients were first line, and four patients were second-line patients. The median overall survival has been reached at 66.3 months. Since malignant melanoma is our lead indication, we have compared these results, even if it's a very small group with 12 patients, with other trials.
In the next slide, you can see the three columns for overall survival and three columns for progression-free survival. The light gray column represent the ipilimumab cohort in the CheckMate 067 trial, and the dark gray column represent the Norwegian Ipi4 trial. As you might remember, when ipilimumab came to the market, it was not reimbursed in Norway. Instead, an observational trial was opened, and patients with the right indications were included in that trial. The protocol for our trial is identical with the Ipi4 trial, except for the vaccine part. As I just mentioned, the median overall survival read out at 66.3 months in our trial. In international trials, 17 months. It's also some trials with a few months more or less than the 17 months, and 12 months in the Ipi4 trial.
For median progression-free survival, we saw a readout at 6.7 months. In the international trials between 2.9 and 3.7 months, and in the Ipi4 trial, 2.7 months. Also, when it comes to response rate on the next slide, you can see. No, sorry, it was not there. We have in this trial also one complete responder and three patients with a partial response. On the next slide, you can see the trials that are active in Ultimovacs as of now. The upper line represents the trial, Phase I trial, where we combine the vaccine with pembrolizumab, as was reported at ASCO last year. Further information from this study will be published and hopefully also presented at an upcoming conference.
As you also can see in this slide, we have an extensive Phase two program with more than 650 patients that will be enrolled on 3 different continents, in Australia, Europe, and U.S. Malignant melanoma is our sponsored trial, and we are collaborating in other indications like mesothelioma, ovarian cancer, head and neck cancer, and lastly non-small cell lung cancer. What is common for all these indications is that the tumors express telomerase, which is the antigen we are targeting with our vaccine. At the bottom line, you can also see that we have a line with the TET platform where we have started a prostate cancer trial to identify the right dose and understand more about safety and immune responses with this platform. On the next slide, you can see our sponsored Phase 2 trial, the INITIUM trial.
As you know, this trial was started almost two years back in June 2020 and recruit patients in the U.S., U.K., Belgium, and Norway. As of yesterday, 137 patients were enrolled in this study, and we expect top-line results in first half of 2023. In this trial, the patients receive nivolumab plus ipilimumab plus minus the vaccine on top, and the primary endpoint is progression-free survival. The patient population in this study are those patients with advanced or metastatic malignant melanoma stage 3B to four. On the next slides, you can see two of the studies we are collaborating in. First, the NIPU trial, which is a trial sponsored by Oslo University Hospital. They collaborate with BMS and us to include 118 patients from sites in Scandinavia, Spain, and Australia.
In this trial, the first patient was enrolled in June 2020. Excuse me. As of yesterday, 78 patients were enrolled in this study. In this trial, we expect top-line results first half of 2023. As you might have noticed, the combination here, nivolumab and ipilimumab, has been approved as a standard of care both in the U.S. and in the EMA region. We do hope that the UV1 vaccine on top will further enhance the efficacy for these patients. To the right, you can see the DOVACC trial in ovarian cancer. It's a second maintenance cancer in patients.
That means that the patients have received two lines of chemotherapy, and if they respond to the second line of chemotherapy, they are put on maintenance treatment. The study is sponsored by NSGO and ENGOT, which is the European umbrella organization for such groups working with clinical trials in gynecological cancer. They collaborate with AstraZeneca and ourselves to include 184 patients from countries in Europe, 10 countries with more than 40 sites. The first patient in this trial was enrolled in December 2021, and as of yesterday, four patients were enrolled in this trial. In this Phase of the study, there's a lot of work to be done with contracts, with discussions with authorities, etc., to set up the sites and get approval to run the study in the different countries.
This is taking somewhat longer time now these days than it used to do prior to the COVID pandemic. We expect enrollment in this trial to catch up as soon as the sites are activated. Top-line results will be guided on in the Q4 presentation 2022. In this trial also, as you can see at the bottom, all patients will receive the PARP inhibitor olaparib, and in the experimental arm the patients will also receive durvalumab and UV1. The primary endpoint in both trials on this page are PFS. On the next slide you can see further two Phase 2 trials we are collaborating in. To the left, the FOCUS trial which are in patients with head and neck cancer that are metastatic or recurrent.
The patients also need to have expression of PD-L1, and that is the indication for standard of care treatment with pembrolizumab. The study is sponsored by University Hospital Halle (Saale). It's a purely German trial with 10 sites across Germany, and 75 patients will be enrolled. First patient were enrolled in August last year, and as of yesterday 18 patients have been enrolled. Guidance on readout from this trial will be given at the Q4 report 2022. The LUNGVAC trial is our last Phase II trial in advanced or metastatic non-small cell lung cancer patients. These will be patients that has PD-L1 expression 50% or above, and without the common mutations in lung cancer. In this study, UV1 will be combined with pembrolizumab in the experimental arm, and pembrolizumab alone in the control arm. This is the standard of care.
The study is sponsored by Drammen Hospital, and most large hospitals in Norway have agreed to participate in this study. 138 patients will be enrolled, and enrollment is expected to start during this first half of 2022. Guidance on readout will be given in the Q4 presentation 2022. In both these trials, primary endpoint is also PFS. On the next slide, you can see that we have also taken a new initiative where we want to include extra 20 patients after the complete inclusion in the INITIUM trial. This is a supplementary study that will be used to further support that the immune response specific to the UV1 vaccine transfer into antitumor activity, and not least clinical benefit for the patients.
In these patients, it will be taken biopsies prior to and after treatment, and that is important to further understand how the activity of the vaccine works in the patients. I would like to stress that these 20 patients are in addition to the INITIUM. It's not part of the primary endpoint that will read out from the INITIUM trial, and it will not affect the timeline for the top-line readout of the INITIUM trial. These 20 patients will not be part of the primary analysis of the INITIUM trial. The inclusion of these patients will start when inclusion of the INITIUM trial is finished. On the next slide you can also see an update on the TET platform.
As you might remember from earlier, this TET platform is an adjuvant technology where tetanus antigens are built together in a molecule, and that molecule can then bind to different peptides that are relevant in different cancers. This is also in the preclinical development but also in an early clinical study, the TENDU trial. The TENDU trial was started in February 2021, and as of now eight patients have been enrolled in this study. In this study there are different dose levels, and we are now on dose level number three. After dose level number two it was a safety meeting that concluded that it was okay to move the dose of the construct up to 960 microgram.
In the TET technology, in the TENDU study, we have these three dose levels. At this last dose level, it might be decided that we will expand to six patients, up to six patients to get further information on immune responses and safety, in this dose, at this dose level. Information from this trial will be very important for the further development of the TET platform, moving forward. If you go to the next slide, I guess this will end my session, and I will leave the word to Hans now.
Yes. Good afternoon. We're now moving to the key financials for the first quarter. As we see, there should be no significant or surprising news related to the key financials. I will walk you through the key messages. Moving to the next slide. Just as some introductory comments, we would like to say that when we look at the main cost component, R&D expenses and IPR expenses, we do see an underlying growth in these expenses quarter by quarter due to an increased activity level in R&D and in the clinical development program. Despite this sort of underlying growth, there are quarterly variations due to milestone payments in particular the large R&D projects.
We'll come back to that a little bit later in these variations. When it comes to payroll expenses, the second most important cost component, the underlying expense level is fairly stable. We also see some quarterly variations here, which is due to the share option program. When we account for the share option program, there will be allowances for social security tax in certain quarters driven by a positive share price development. Also in periods with a negative share price development, there will be a reversal of such allowances. This will influence the expenses quarter by quarter. We'll come back to this when we look at the specific numbers.
We have by the end of the first quarter, 2022, we have a total cash position now NOK 523 million or roughly $54 million. This provides an expected financial runway to the first half of 2024. On the next slide, we can see that the total operating expenses in Q1 was close to NOK 32 million. The total loss for the quarter was NOK 37 million or NOK 36.6 million. When we look into the different cost components in a bit more detail, we see fairly stable payroll expenses. As I mentioned in the introductory remarks, there was some costs related to this share-based compensation.
A reversal of an annual Social Security tax allowance that actually gave a slight reduction this quarter compared to the same quarter last year. If we adjust for that, we see that the underlying increase in payroll expenses is roughly NOK 1.5 million higher this quarter than the same quarter last year, and this is driven primarily by 2 additional full-time employees. If we move on to the R&D and IPR expenses, we see that we had slightly lower costs in Q1 2022 compared to the same period in 2021. Generally, as we have stated in earlier quarters as well, we expect an increase in R&D expenses compared to this level as we progress the R&D activities and the clinical trials, including CMC development.
We had lower than expected costs this quarter, and I'll come back to that a little bit later. On other operating expenses, we had a slight increase due to increased activities within business development and investor relations, and also some increase in travel expenses as we now can start going a bit more on conferences and have more physical meetings than we have had during the pandemic. Looking at the operating cash flow on a quarterly basis, we see that the negative operating cash flow has increased steadily over the last quarters. Again, this is driven, of course, by the increased activity level within R&D and clinical development.
What is worth mentioning when it comes to Q1 2022 specifically is that we had by the end of 2021 quite significant outstanding account payables in the order of NOK 23 million, and this was converted to a net cash outflow when these bills were paid during the first quarter. It means that for Q1 2022 specifically, there is quite a big difference between the operating expenses amounting to NOK 32 million and the negative operating cash flow amounting to roughly 45 million in minus. Just as information. The last slide on key financials. There I would just like to emphasize again these variations from quarter to quarter. As mentioned before, the total expense level in the first quarter was around NOK 32 million. The same level as one year before, the first quarter of 2021.
When we look at the underlying development during 2021, we had an increase in total operating expenses from NOK 31 million in Q1 up to NOK 51 million in Q4 2021. As I said, this quarter's expense level is lower than expected. We are guiding that the financial runway of the company will be to the first half of 2024. This implies that the quarterly expense level should be on an average for 2022 and 2023 should be more like the Q4 2021 cost level or slightly above that. That's sort of the rough guidance. It's hard to estimate exactly when these expenses in the different projects actually fall.
It's easier to estimate the total cost than actually specifically say which quarter they will come. This is as we have said several times before. With that, I will move over to the next slide and leave the word to Carlos to take us through the news flow. Thanks.
Thanks, Hans. Thanks, Jens. You know what to expect for the rest of the year and next year. Well, as you know, we had a very busy 2021, but now for the rest of 2022, we expect, as I mentioned, that now in the second quarter to communicate when the first patient in the LUNGVAC study is enrolled. A very important data will come in the third quarter and fourth quarter still related to the UV1-103 study in combination with pembrolizumab melanoma. We are gonna have the two-year overall survival update for all 30 patients in the study. And this is a very important endpoint. Overall survival is looked at very carefully by the authorities, so we expect to provide that update in the third quarter.
As you know, the first quarter, 20 patients started earlier, and we will have the three-year overall survival update during the fourth quarter. Very important data, but of course, you know, the first half of next year is gonna be, you know, the period that everybody is waiting for. I want to emphasize here, as Jens mentioned, that, you know, we have no reason at this moment to change our guidance of expecting the top-line results for INITIUM and NIPU during the first half of 2023.
Of course, you know, as both DOVACC and FOCUS started later, we will see how these studies progress during the rest of the year, and then we will be able to give you a more, you know, a better guidance on the results expected for when during with the Q4 report of 2022. Also at the same time see how the LUNGVAC study progresses. You know, very exciting times ahead, and we all remain optimistic and dedicated to make sure that these patients continue to be enrolled. In the next slide, you know, I just want to again, you know, give a summary and the key takeaways from the report.
Important INITIUM and NIPU continue on track to, as expected, deliver the top-line results during the first half of 2023, with good patient enrollment despite the challenges of the COVID pandemic. The extended patent protection in the U.S., very important for extending the commercial potential of UV1. Very good to see that patients, some patients in the study continue to, you know, improve in terms of their status and moving from partial response to complete response. That is a total disappearance of the tumor, and that we have now 33% complete response in the UV1-103 study. As Jens mentioned, we have reached now the median overall survival of 66 months for the study in melanoma in combination with ipilimumab.
It's a small study, but it's quite a remarkable improvement in the overall survival. As you know, we have been very busy last year and this year so far in publishing results, presenting at medical conferences. You know, one was just a couple of days ago. We expect for the rest of the year to continue having additional presentations and publications, and particularly with more detailed data on the 103 study. TENDU continues to progress in the terms of study, but not so visible, we continue to have different activities supporting the TET technology, both in terms of preclinical studies and CMC activities.
In a very difficult time for biotechs, as you all know, last year and this year so far, we are very pleased that we have a strong cash position that really allows us to focus on the business as the financial runway to the first half of 2024 allows us to be financed through the period where we are going to expect all the results from the clinical trials. A very good place to be. You know, I just returned from a conference, and this was really one of the key topics of discussion is how the environment is so challenging for biotechs that at this moment need to raise money and how difficult that is both in Europe and in the US.
We are very pleased that with all of your support, we were able to have quite a very good capital raise, you know, past October, and we have now this situation where we are financed for the first half of 2024. With this, I would like to, you know, end here the more formal part of the Q3 reporting presentation, and opening now the floor for the Q&A. Again, I want to thank everybody before we start answering questions for all the time and efforts that you took in sending us several questions even before today. Hans?
Yes. Thank you. We, as you say, Carlos, we appreciate that we have received both some questions in advance, and also now during the presentation, and we are happy to receive more if you should have so. I can start off, Carlos, by asking one question here. You have not yet completed the enrollment in INITIUM. Will this influence the expected readouts?
It's a very good question, and I really appreciate receiving this question because allows us to clarify a little bit, you know, how this process works. Before I directly answer this question, let me tell you a little bit about the differences in how we expect to read out the trials. We have 5 Phase II trials. Four of them are what we call event-driven. The study is concluded from a perspective of the endpoint when a certain number of events are reached. I will come to that. In one study, in the FOCUS trial, is what we call a landmark study, where we have a specific time after the last patient is enrolled where we read the results.
In the FOCUS trial, for example, is six months after the last patient is enrolled, you know, we stop then and look at the differences between the two groups. In specific study like FOCUS, the time of enrollment of the last patient is of course very important because it's going to define when these, in this case, six months period is gonna end. In all of the other studies, because they are event-driven, let's pick up on the INITIUM one. We analyze the data and compare the data between the two arms when 70 events happen, and events are defined as when the patients progress or when the patients unfortunately die.
When 70 of these events happen in both groups, then we stop the trial and compare the data between the two arms. As you can see, because this is event-driven, not landmark-driven, it's really not as impacted by when the last patient is enrolled. We still expect, you know, because we only have 17 patients left, that these will be enrolled, you know, in the next couple of months. But this is not important to define when the 70 events are gonna happen.
You know, based on looking at historical data and the statistical plan that was put in place, you know, by a statistician expert, industry standards discussed with the investigators, with the authorities, we, you know, establish that, you know, this will be happening in the first half of 2023. In reality, can happen before, it can happen a little bit late. You know, we don't know, but that is also not important. What is important is that when the 70 events happen, you know, we can then compare the results between the arms. You know, it was a long answer, but I think it's important to explain, particularly for the ones that are not so familiar, this difference between event-driven trials and landmark trials that the
In reality, the fact that we still have some patients left is not impacting our expectations for results, top-line results to come in the first half of 2023.
Thanks, Carlos. Another question related to patient enrollment. How does the patient enrollment look going forward, given that the corona situation doesn't drastically change for the worse?
Well, you know, hopefully for all of us, you know, in not only for patients in clinical trials, you know, the situation will not get too worse than what it is now. Again, it's been moving more under the radar, but it's still there, and you see in some countries expecting, you know, maybe another wave more towards the late fall, the winter. Hopefully, particularly for our the first studies, will not have an impact. You know, we don't see that impacting. The fact is that, yes, the situation is not yet normal. As I mentioned in doing the presentation, in some countries, some hospitals have reduced personnel and this delays, you know, the fact that they cannot follow patients, so they are a little bit delayed.
You know, I think we are very pleased that despite all these challenges, we continue to enroll an important number of patients, and these are clinical trials. You know, this is not a production of automobile pieces, you know. Say in some months we have more patients, in other months we have less patients. The fact is, it's, you know, very pleasing to know, to see is that patients continue to be enrolled. Again, only very few patients are left in the initial study.
Thanks, Carlos. We have one more question related to enrollment. Regarding the DOVACC trial, you said that it takes longer now than in the past to get sites active. Can you give us a feeling for how many sites out of the planned 40 sites that are truly active and can recruit patients as of now?
Jens, do you wanna take this one?
Thank you for the question. What I can say is that the first site opened in December to include patients, and there are different territories where sites are starting to open, and in other countries it might take a little bit longer. The exact number of sites that are open right now I cannot answer right here. The ambition of this group, the NSGO group and the ENGOT society, is that when they open these trials, they are very eager to enroll patients and very dedicated to the trial. My experience with this group from earlier studies with them in other companies is that when sites are open, enrollment will be quite good. Let's hope that is also the fact for this trial.
Thanks, Jens.
Okay, thanks. We have a more general medical question, so I guess that's that may be to you, Jens. You recently reported 91% UV1 specific immune response in the Phase 1 UV1 ipilimumab trial in melanoma, while the impact on tumor size, so-called objective response rate is 33%. Could you please elaborate on the difference between these numbers when it comes to immune rates versus immune response versus objective response?
Yes, I can try that, and, I will try to make it, somewhat simple. Immune response, what is that? When we are vaccinating the patients, with our peptides, we are doing that to get with an adjuvant in a way alert the immune system that something has come into the skin. What we hope is that the immune system will be interested in the peptides, take them up, and present them to the rest of the immune system. In our first three trials, as you have mentioned now in the IPI trial, we saw an immune response of 91%. That means that in all bodies, prior to, any disease, you will have T cells that can recognize almost anything in the world.
That is why we can cure ourselves from the COVID disease, for example, which have never been in humans before. What we are doing when we are vaccinating with these peptides, we do think that there are T cells in the body that can recognize these sequences, and we show that in 90% of the patients, these T cells exist. When they bind to the peptides, they will start to divide, so we will have a lot of those recognizing telomerase. An immune response mean that you have amplified or expanded the exact T cells that recognize one or all of the sequences in our vaccine. There you have the immune response. There is another axis here, the tumor. How to get the T cells, expand the T cells into the tumor.
20 years back, those who remember vaccine trials from those days, we saw very good immune responses but little clinical efficacy. What is new on the market now is the checkpoint inhibitors. Over the last 10 years, we have seen several large clinical trials that have shown that if you add a checkpoint inhibitor in an indication, a lot of the patients have efficacy from that checkpoint inhibitor. What is actually happening is that the tumor is opened or made available for the existing immune system. That doesn't happen in all patients. As you know from these large KEYNOTE and CheckMate trials, not all patients are cured with the checkpoint inhibitors. The PD-1s and PD-L1s don't help all patients.
Even if most patients will have the right T cells, they cannot do the work in all patients because there need also to be effect from the CPIs, that is our hypothesis, to open the tumors for these T cells. What we do see or what we believe that we will see with the vaccine is that when you are treating patients and they have some initial effect from the CPIs, a vaccine can further push the response in the individual patient to a better level. We have seen that, of course, with small numbers in the 103 trial, where a larger fraction than expected of the patients have a complete response as compared to partial responders. It's actually more complete responders in that trial than partial responders.
Immune response on one side, that means that you have managed to expand the right T cells. If they work or not is also dependent on the effect of the checkpoint inhibitors you are combining with. The checkpoint inhibitors doesn't help all patients, therefore you see lower response rates than the immune response.
Thanks for a thorough answer, Jens. We have a UV1 specific question. What's the rationale for giving 8 cycles of UV1 in your trials compared to several other cancer vaccine companies that give more cycles of their vaccines during treatment?
I guess there are two answers to this, one medical and one more like marketing. I start with the medical part. In the three first trials we showed you today, the three early Phase one trials, it was allowed to vaccinate the patients a lot more than we do in the clinical trials today, up to 16, 17 times. What we saw and what it has also been presented at the CIMT meeting now just recently is that for most patients they will have their response or expansion of T cells, as we just discussed, at an early stage. Most patients at a median of six vaccination will have their immune response. We do not think it will compromise on efficacy to reduce doses with the UV1 vaccine.
In the UV1-103 trial that we reported last year at ASCO, it was eight doses of the vaccine. Even if that is not a randomized trial, we have the efficacy signals at least as we have presented earlier from that trial presented.
Yeah, thanks Jens, because there's definitely a medical rationale, but there's also a commercial rationale. As you know, you know, and this has been, you know, discussed several times with big pharma, you know, we want to have as less treatments as possible so that patients don't need to go to the hospital so many times. Of course, we have the benefit that we administer intradermally, so it's not a very complex treatment process. But it's clearly preferred that, so the less number of treatments is the better from a medical practice and in terms of a commercial perspective because it's more convenient for the patients.
You know, we have the medical rationale, but we also have the more commercial rationale that you know, increases the adherence of the patients to the treatment, reduces the costs, and facilitates the treatment.
Okay. Thanks. We have a more general question on clinical trial design. Why is it important to have comparative studies, and how did you define the statistical plan for your Phase two trials?
Well, Jens, maybe I can start because, you know, I touched bases already before. As I mentioned, you know, the statistics are defined from the very beginning, and they are based on previous results that give an indication what is the expected benefit of the control arm, the standard care in our case, and then what will be the expected benefit. These statistics are put in place by the Ultimovacs team, an expert follows industry standards. These statistics are discussed with investigators, then with the authorities, with the ethical committees. It's a long process to really agree and establish what is the statistic plan. This is very important.
It's particularly important, in fact, in the studies, all our Phase 2 studies, because we have these control arms. This is sometimes not appreciated that although these are more complex, more costly, it's extremely important. As I mentioned, you know, I was just at a conference where this was thoroughly discussed in one of the panels that a lot of biotechs run clinical trials without a comparative arm. What is usual during the Phase 1? Some companies move to Phase 2 without comparative arm, and then, you know, there's no way of really assessing the benefit. We decided to do it from the very beginning as a comparative study. What this does give us is that, you know, each study is different.
The past studies were run by different groups in different countries, different patients, so it's extremely important to have a control arm because then you have the same centers enrolling both patients, you know, the same type of patients with some variability. It's extremely important for, you know, in terms of discussing with potential partners, with the authorities, that you have a control arm that you can compare to. That is also the reason why it's important that the statistics defined in your study allow to find that difference if it exists. I don't know, Jens, if you have any additional comments, you know?
No, I just have to say I'm completely agree with you. It's very important with this randomized trials. We use the best treatment in both arms, the standard of care. On top of that you're adding the experimental drug, in this case, the UV1 vaccine. Of course, different trials, you can have different sizes of the trial, you can have different statistics of the trial. Our trials is like the common Phase 2 trials, size between one and 200 patients, a design which allows you in a way to move forward in a Phase 3 trial upon positive results, or move forward with subgroups if the trial is inconclusive.
If you look to the literature, and you for example would like to see what kind of efficacy will a pembrolizumab give you or nivolumab or in a specific indication, you will see very different results. That is exactly what Carlos said. Different hospitals, different routines for taking care of safety events, different time periods, et cetera, will make a huge impact on trials.
Okay. Thank you, Carlos and Jens. Next question. Will readout in the first study imply the same result in the other four studies? Jens?
Well, this is somewhat connected with what William were discussing with the immune responses and responses as such for the patient. Of course, if there is a positive readout in the first study, it will give us some proof of concept. We have in a way shown that adding the vaccine on top of checkpoint inhibitors will in that indication with that population lead to a better outcome for the patients based on the statistics in that trial. As you remember from a few minutes back, different indications will have different efficacy from checkpoint inhibitors, for example. In some indications it might be so that the adding something to the checkpoint give a little extra effect, while in other indication it could give a tremendous effect.
All in all, a positive readout in the first trial will be very good for the proof-of-concept thinking. Let's hope that most patients in this different indications will benefit from the vaccine on top.
Just to comment there because, you know, you have the other reverse, you know. If one of the studies, you know, doesn't reach the positive readout, it doesn't mean that the other ones are also not have the same what we call not so positive results. It's really gonna depend on indication by indication. As Jens stated, you know, a positive study is a confirmation of the rationale to add UV1 to the checkpoint inhibitors, and very valuable.
Okay. I see that time is running with many questions today. Just a last quick question on a related subject. What kind of data will be communicated at the time of readout or top-line data?
You know, it's important here really, and thank you for the question, because you know, we are gonna have a lot of results, and all these data will be analyzed after the events, let's pick up INITIUM, are reached. It's important, as you already know, that we preserve several part of the data to be published or presented at medical conferences, because those are very important for the company. What we will disclose is normally what we call top-line results that are referred to the primary endpoint, in this case, PFS. You know, is there a difference between the groups and this difference is positive? Basically, is the study positive?
That's what we will communicate, and that is the key part. A lot of the details, as we already communicate in the past, and I think our shareholders understand that are extremely valuable to present at a conference and to publish.
Just to add to that, on the safety side also.
Yeah, of course.
on background of the safety in the two arms. That will be very important for us to understand both the efficacy and safety side. As Carlos said, these results are very valuable for us in the further discussion with authorities, with the doctors that hopefully will be part of a Phase three trial moving forward. It's a lot of results and only the PFS will be presented from the efficacy side upon an end of study.
Okay. A very specific question. Are patients in INITIUM and NIPU censored for data analysis if they proceed to another treatment before reaching PFS?
First, the data from the INITIUM trial, they are not in our hands. That is of course something that is common in the pharma industry. It's something called central review. That means that there is a third party for the hospitals as well that read all the images from the patients. There is a set of rules from the FDA and also in the EMA region how to read different scenarios. Some patients can disappear from the study. They move to a different place. Some patients might have unexpected surgery, radiation, et cetera. All of these things are taken care of and is in our study done in the same way as in the other clinical trials.
It will be difficult to answer specific questions because there are so many nuances to each scenario, but this is taken care of by a third party and is blinded for us. We do not know anything about the responses in the different patients.
Jens, it's fair to say, you know, that basically all these events that you mentioned, including a patient getting other treatment, then will be protocol violations. The patients are still a part of the study but will not, you know, will be handled differently. Yeah.
That is correct.
Thanks, Jens. We have three questions related to the supplementary study to INITIUM. I think we can probably cover them together. I'll ask them together. Can you elaborate on the supplementary study to INITIUM and which readouts you will pursue in that trial? How will these specific readouts add to your understanding of UV1-specific immunity? Let me just add two more questions. Will the INITIUM supplementary study impact the INITIUM study in any way? Last, do you have a timeframe or results from the 20 extra patients to the INITIUM study?
Jens, if you don't mind, I address the last two and then I'll leave you the science part, you know. I want to be clear that the supplementary study is very important. You know, Jens will cover that, but I also want to be clear that the supplementary study will not affect in any way the INITIUM study. Not only the timing to analysis to the results, but also the following steps in terms of INITIUM. INITIUM is 154 patients and will progress.
The supplementary study will bring very valuable data that I will let Jens elaborate and, you know, this will be running and the patients will start to be enrolled, as mentioned by Jens, immediately after, you know, the INITIUM study completes enrollment. You know, the data at the moment will be too premature to give any guidance when the data is available. You know, we will inform as usual our shareholders, interested parties how that evolves. It has no impact on the INITIUM study, not only in terms of the results, enrollment, but also how the data is analyzed or as we discuss with the authorities these results. For the rationale why we are doing, I give the word to Jens.
Well, yeah. It's actually quite important. Of course, I'm a positive guy here. We expect that, for example, the INITIUM trial is positive and we move on with the Phase 3, and that is also positive in this scenario. We are applying for authorization in the melanoma indication. That is a huge job. It's something called the eCTD. That is the file you are delivering to authorities, and in that file it's possible to give information on the different levels. The clinical trial as such is the most important information. The safety and efficacy from the clinical trial will lead to a large proportion of the conclusion from the authorities. They will also like to have more information.
Is it a association or even correlation between, for example, complete responders and things you can see in the tumor? What we are doing in these 20 patients is that there will be taken biopsies prior to start of treatment and after end of treatment. What we would like to see is that we can have some evidence that the vaccine first give this immune response that we have discussed. Further, that these T cells that we expand are able to move into the tumor and even show that those T cells can kill tumor cells. You can show that either directly, that is very complicated and has been done very few times, or you can do it indirectly.
One indirect way to do it is that you can look at the repertoire of T cells that are present prior to treatment versus after treatment. Several other methodologies to, in a way, make it more reasonable to believe that there is a direct association between the vaccine and the effect you see in the clinical trials. In that way, you will be able to have a discussion with the authorities, not only based on the clinical outcome, but also evidence from the R&D side. That is very valuable in such discussions and will also be helpful in guiding moving forward when you select the exact indication, et cetera.
Very valuable for us in the guiding process and also for the authorities when it comes to decisions around approval of the drug.
Okay. Thanks, Jens. We also had a question related to timeframe for the results.
Yeah. I think that as I comment, you know, we will start enrolling patients immediately after the INITIUM is finished. We will be providing a better guidance. These patients will go through the same type of protocol, but we'll have additional exams that were not included in the INITIUM study. When these patients are enrolled, then we will be able to provide, as usual, a more clear guidance in terms of these results. As I mentioned, these are not going to be affect or be affected by what happens with the INITIUM clinical trial end results.
It's also one more thing I would like to mention is that the last biopsy here will be taken after end of UV1 treatment. That is very important because in this group of 20 patients, we would expect that some will have complete responders and some will have a partial, and some will not have a response at all. It's the difference between these different groups that is actually interesting when it comes to the R&D. What is the differences clinically, and then can you see the same differences in the sub-study analysis?
Okay. Thank you. We now have two questions left, so thanks for the patience from everyone. Does the patent extension for UV1 in combination with checkpoint inhibitors include extended protection also for UV1 combined with more than one checkpoint inhibitor?
Yes. This is a UV1 extension is UV1 in combination with any of the checkpoint inhibitors. It doesn't matter how they are combined and is very valuable.
Good. Thanks, Carlos. We have one last forward-looking question. Depending on the different scenarios materializing from readouts in first half of 2023, what are your preferred commercial pathways moving into Phase three, both from a risk-reward perspective and also from a capital need perspective?
You know, we have been open about our strategy. We basically are moving and doing everything as a company to move into Phase three by ourselves. Of course, this will require in the future additional capital raises, but of course, this will be on the back of positive data. We in parallel, as we have been mentioning, are in regular talks with companies that will be the interested ones if the data is positive.
The reason why we're looking at that is because, of course, as a biotech, we could move into Phase three with one, two indications, while a partner with more financial capabilities will be able to have all the data and the product that is in the commercial process by that time to move into several indications in parallel. I think the important part is to say, "Look, we are moving forward," and if that is positive, we'll be preparing for all the meetings with the regulatory authorities to define the next studies to discuss with the authorities if that is very positive, the possibility of a conditional or accelerated approval.
At the same time as we move that is our responsibility also, discuss the results with potential partners that could expand basically, you know, increase the magnitude of a Phase three program.
That was all questions.
Okay. Good. Thanks, Jens. Thanks, Hans. And of course, primarily, thank you everybody for being with us, the patience to listen to what was a very extensive Q&A. You know, we are happy that there is a lot of interest from all of you, and thank you again for sending all the questions. As you know, we look forward to continue communicating with you and we will be organizing some events to get closer to you and give you the opportunity to ask additional questions.
also for the rest of the year, as part of our plan to increase the visibility of Ultimovacs among the scientific community, of course, the potential partners, what we do on a consistent basis, but also to increase the visibility to other investors, not only in the Nordic countries, but also Europe and the U.S. again, thank you so much for all your time and your interest and questions, and we will stay in touch. Thank you, everybody.