Good morning, everybody, and welcome to the fourth quarter 2021 Ultimovacs presentation. My name is Carlos de Sousa, and I'm the CEO of the company, and together with me I have two colleagues, Jens Bjørheim, that is our Chief Medical Officer, and Hans Vassgård Eid, that is our Chief Financial Officer. Together we will be covering the key results from our fourth quarter and then also, as usually, we will be followed by a Q&A section. If we can move to the next slide. I need to show you this and then the next slide. I will start with highlights. Moving to the next slide. The fourth quarter was a very successful quarter. In reality basically replicating the great success we had for the full year 2021 at different levels.
In this quarter we had a good clinical progress. We had increased patient enrollment, primarily in our two more advanced studies, INITIUM and NIPU. Ultimovacs as a company has coped quite well with the challenges caused by the COVID-19. In reality we are updating our guidance, but these are just minor adjustments for when we expect to release the top line data for INITIUM and NIPU. Very important for the company in this quarter we received also from the FDA, the US drug regulatory agency, Fast Track Designation and also Orphan Drug Designation for our lead indication metastatic melanoma. Very important in our strategy to diversify and really collect data in as many indications as possible in different combinations. We also announced the initiation of a new study in non-small cell lung cancer.
Of course, Jens will cover more details of all these studies. We also had a very successful capital raise, significantly oversubscribed of NOK 270 million. You know, we continue in this quarter to have further encouraging results already presented as you know earlier in 2021 during ASCO. It's good to see that our study in melanoma in combination with pembrolizumab continues to deliver encouraging results. As you know, we have a second platform, the TET platform, with the first study, the TENDU study, having initiated a year ago, and that study continues to progress quite nicely and no safety concerns have been observed in the first two cohorts of the study. Again, Jens will cover it in more detail.
In the next slide, I can give you an update on are we progressing with enrollment of patients in our broad clinical development program. We are very pleased that the enrollment of patients has really picked up. This is always a challenging quarter, not only of course because of the COVID situation in multiple countries, but also because includes a period that is normally slow around Christmas. INITIUM we have now 120 patients out of the 154 that are the total patients. We really enrolled 29 patients since the last the Q3 report. Very good pick up in enrollment. NIPU are very positive too.
We have now 66 patients out of a total of 118, and this is 21 patients more than are reported in the Q3 report. DOVACC, that was announced as started enrollment in December, is now two patients. And FOCUS is also now 10 out of the 75 patients compared with five in the previous report. As you traditionally know, we continue to be transparent. In each quarter we will continue to give you an update on enrollment numbers for all these studies. You know, we are optimistic and we see a pickup in the number of enrolled patients, but we need to continue aware that the pandemic and now probably moving to endemic situation is still not over.
We saw primarily that the big impact now is not so much on the patients themselves, but on a lot of health personnel that has to get sick. You know, it's not serious, but they are away from the departments and this has an impact on the number of people that can work at the departments. That's where we have seen most of the impact, together also in some studies like DOVACC and FOCUS on initiation of new centers because people are away from work. If we move to the next slide. We have now over 75% of the patients in INITIUM enrolled and over 55% of the patients in NIPU enrolled.
As you saw and I showed to you, the enrollment rate has increased quite nicely in both trials in this last quarter. As you know, we have had a guidance for disclosure of the top line results in these studies that were for the second half of 2022. This guidance was established in 2019, before even, of course, you know, almost three years ago, and the world knows the situation we were gonna be getting with the COVID-19 pandemic. We believe that now with an updated guidance of top line results from second half of 2022 to first half of 2023, you know, we can consider this is really a minor change in the guidance. If we move to the next slide.
Both DOVACC and FOCUS trials are still in the early stages of new hospitals being activated. As I mentioned, this has been a part of the activities that is taking a little bit longer because from the perspective of authorities, they're having to approve ethical committees in hospitals in different countries, so it's taking a little bit longer, but you know, we expect this to progress. We have guided that we will have top-line results during 2023. In LUNGVAC, as you know, our new study that we announced just very recently, we expect the first patient to be enrolled during the first half of this year, and the expected results by the end of 2024.
For all of these studies, you know, different levels, you know, they are still very early in the initiation and running of the studies enrolling patients. We believe it will be in addition to what we disclose to you. You know, we like to disclose only facts. We will provide you a guidance, an updated guidance with the fourth quarter report in 2022, so basically in one year time. Of course, we will continue to update you every quarter with the number of patients enrolled. If we move to the next slide.
Very pleased as a company that we continue to have high interest from key opinion leaders and very important oncology centers that want to collaborate with Ultimovacs and test our vaccine UV1 in different indications. This is lung cancer is a big indication, and we were very pleased to announce a new study in non-small cell lung cancer in combination with pembrolizumab. As I mentioned, we expect the first patient may enroll during the first half of this year, and Jens will be giving you some more details. Part of the reasons, you know, of course to support initiation of the study and further operation and also to continue developing the TET platform we raised capital in October 2021.
This is a capital raise of NOK 270 gross million, and that was very successful. You know, it was significantly oversubscribed, and Hans will give a little bit more detail. The important here is that, basically now as a company we have a new runway that is enviable in this during these times of challenges to the whole healthcare and particularly biotech industry. We have a new runway that runs into the first part of 2024. If we move to the next slide. As I mentioned, we received Fast Track Designation.
You know, this was part of this, was disclosed in the last report because it happened before the Q3 report, but I just want to emphasize this is a recognition from the FDA that the data that we presented to them, both in combination with ipilimumab, one of our first studies, and in combination with pembrolizumab, the study that is still running, were of sufficient quality for the FDA to grant us Fast Track Designation. What, of course, is a recognition by the authorities but also has benefits for the company because it allows us to have closer interactions with the authorities if the data is quite positive. Also, makes us eligible for accelerated approval priority reviews.
This is very positive to the company and really confirms our confidence in the therapeutic potential of UV1. The next slide. You know, we also received in December Orphan Drug Designation. The next slide, Hans. Orphan Drug Designation is also very important for the company. The benefits are primarily after approval because really gives us extra seven-year market exclusivity in the U.S. after approval. This is, of course, as you can imagine, very important. Also for small biotechs like us, the exemption from the FDA application fees that are quite significant in the range of $2 million-$3 million. These are all benefits and again, a recognition that the data supports, you know, the grant of this designation.
As you know, metastatic melanoma is UV1 lead indication, and we are currently having additional studies in each of these ones in phase II in metastatic melanoma, the INITIUM study. You know, in this study will be giving you more details and together with all the other ones by Jens. If we can move to the next slide. I will give now the word to Jens to give you all an update on what's happening with all our clinical trials.
Thank you, Carlos. Could you please move to the next slide, Hans? As Carlos just stated, we received a Fast Track Designation in our lead indication last quarter, and those designations are based on data from two phase I trials. In our lead indication, we have already conducted two IND trials, one with UV1 in combination with the ipilimumab and one with UV1 in combination with pembrolizumab. We have reported on results from both these trials earlier. The UV1-ipi trial is a trial that has been under observation for several years already, and we have published data from this trial in Frontiers in Immunology in May last year, and also an abstract at SITC's annual meeting in 2021.
For the UV1 pembrolizumab trial, we presented data from this trial at ASCO last year, 2021, and also there has been updates in press releases during the autumn. On the next slide, you can see, just as a reminder, the efficacy data from this last trial. In total it was 30 patients included. On the safety side, the safety profile was as expected for pembrolizumab monotherapy alone. On the efficacy slide, you can see the results here. This is as of a readout mid-autumn last year. nine complete responses, eight partial responses, two with stable disease, and 11 patients with progressive disease. For the median progression-free survival at last readout, we had 18.9 months for the first cohort in this trial, and the second cohort has not reached a readout as of mid-autumn.
Those patients were included in the study at somewhat later time points. For the overall survival after 1 year, we saw between 85% and 90% overall survival, and the first cohort in that study showed 80% survival after two years. This data, both from this trial and the UV1-ipi trial, are data that were used by the FDA to give us the Fast Track designations. We have already moved into phase II with our lead indication. On the next slide you can see the INITIUM trial. This trial is a phase II trial. It's a randomized trial, two arms. In both arms the patients receive nivolumab and ipilimumab, and in the intervention arm UV1 on top. First patient in this trial was enrolled in June 2020, and we enroll patients from the U.S., U.K., Belgium, and Norway.
As of 16th of February 2022, 120 patients are enrolled in this trial. We expect top-line results first half of 2023 after 70 patients have progressed or died, so-called progression-free survival. This is an endpoint-driven trial, so we are waiting for these 70 endpoints to occur, then we will close the database and make up the material. On the next slide you can see that we are also involved in several other trials. The upper two lines represent our lead indication, melanoma, which we have just now discussed. In the red box you can see that we have also a part in different other indications. We are contributing in four other phase II trials in different indications. The common denominator for all these indications is that the cancers are expressing telomerase, so we think that the UV1 vaccine will have relevance in.
for these patients. We are in mesothelioma, ovarian cancer, head and neck cancer, and non-small cell lung cancer, and I will come back to these trials over the next slides. At the bottom you can also see, as earlier in the TET study, we have the TET program, which is a new adjuvant technology, and in February last year we started the first-in-man trial in prostate cancer to identify the right dose, understand more around immune responses and safety with this new approach. On the next slide you can see the two first phase I, II trials we are collaborating in. To the left, malignant pleural mesothelioma. This trial is in patients that will receive nivolumab and ipilimumab, and on top of that UV1 in the intervention arm.
This is a trial that is sponsored by Oslo University Hospital, and they collaborate with Bristol Myers Squibb and with us to include 118 patients from Scandinavia, Spain, and Australia. First patient in this trial was enrolled in June 2020, and as of 16th of February, 66 patients were included in this trial. Expected top line in this trial is first half of 2023 after 69 patients have progressed, or died, or have reached PFS, progression-free survival endpoint. This trial is an endpoint-driven trial, so we are waiting for these 69 endpoints to occur before we close the trial and make up the material. To the right, you can see the DOVACC trial. That is a trial in women with ovarian cancer. The exact indications are those women that have a BRCA negative cancer, and they have received two lines of chemotherapy.
After the last line of chemotherapy, they haven't responded to that chemotherapy, and they are given the intervention. You can see it bottom to the right as maintenance treatment. In this study, there are three different arms. All patients receive olaparib, the PARP inhibitor, and in arm C, they also receive a PDL1 antibody, durvalumab, and also the vaccine on top. The sponsor of this trial is NSGO, that is the Nordic Society of Gynaecological Oncology, and also the umbrella, ENGOT, which is the group working in Europe with the women cancers. They collaborate with AstraZeneca and us to include 184 patients from more than 40 sites in more than 10 European countries. We are very happy that this study now has started to recruit patients.
First patient were enrolled in December 2021, and as of 16th of February, two patients are enrolled. We will guide the update when this study will read out during the Q4 2022 report. Also in this trial, there is an endpoint-driven design of the trial, so we are waiting for a predefined number of endpoints before the database is closed and the numbers are calculated. On the next slide, you can see two other phase II trials. To the left, the FOCUS trial, which is in patients with head and neck squamous cell carcinoma. This is patients that are metastatic or have recurrent disease, and they have a PDL1 positive cancer. This is the indication for pembrolizumab as standard of care in these patients. The study is sponsored by University Hospital Halle (Saale) outside of Berlin.
It's a purely German trial with 10 sites that will include 75 patients in this study. First patients were enrolled in August 2021, and as of 16th of February, 10 patients are enrolled in this trial. The guidance for top-line results will be updated in the Q4 2022 report. The design in this trial is somewhat different from the other trials, as in this trial there is a landmark endpoint, not these endpoint-driven studies as we have discussed on the last slide. A landmark endpoint means that in this trial, all patients need to pass a predefined number of observational months. After six months, after last patients have been included in this trial, the database will be closed and the data will be analyzed.
In the LUNGVAC trial to the right, in advanced or metastatic non-small cell lung cancer, the patients will receive pembrolizumab in the control arm, and pembrolizumab and UV1 in the interventional arm. This is a Norwegian trial. It's sponsored by Drammen Hospital with Terje Brustugun as principal investigator. It has been a lot of interest around this trial and all major hospitals in Norway will participate to include 138 patients in the trial, and first patient is expected to be enrolled over the first half of 2022. Also for this trial, it will be a guidance on top-line results in Q4 2022. As for the first trials, in this trial, this is an endpoint-driven trial.
We are waiting for a predefined number of endpoints to occur before we are closing the database and analyzing material. On the next slide, you can see the TET technology platform and the TENDU phase I trial. The TET technology is a different technology from the UV1 technology. In this one, we are developing an adjuvant tetanus adjuvant technology where tetanus antigens are built into the molecule to work as an adjuvant in the vaccine. We have started, as I said, a TENDU trial. That is a trial in prostate cancer patients where we use prostate cancer-specific antigens, and this is a first in man trial where we are trying to identify the right dose to give to patients moving forward. We have enrolled six out of nine patients.
We have enrolled all patients on the first two dose levels, and we are currently open for inclusion on the third dose level. This trial will be important for us in understanding the safety of this new concept and also to understand the immune responses produced and safety profile that this molecule will give the patients. This will end the medical part of the session here now. I'm moving over to Hans and financial update.
Thank you, Jens, and good morning. The next section will be on the key financials and the news flow going forward. On this slide, we discuss aspects of the share issue we performed in the fourth quarter. As Carlos mentioned, we announced the fifth phase II trial in non-small cell lung cancer in October, and that triggered a capital raise where we raised NOK 270 million. This time was in a market where we sort of increasingly saw challenging capital markets, not least in the biotech sector. We were very pleased to see that the capital raise was highly successful with significant oversubscription. More than 100 investors took part in the private placement, and we continued to see strong support from existing shareholders.
The existing shareholders, they took around two-thirds of the private placement. But also in addition to the existing shareholders, we saw an increased international presence among participating shareholders, so we increased the geographical footprint of the shareholder base through this private placement. The net proceeds of private placement will be used for the LUNGVAC trial. In addition, we will invest further in bringing the UV1 platform into phase III readiness and also further develop the TET platform. Based on current plans and expectations, the cash we have now will provide a financial runway to the first part of 2024. On the next slide, looking at key financials for 2021 and for the quarter.
We saw that for the full year, we had total operating expenses of NOK 164 million, and that is up from NOK 124 million in 2020, so it's an increase of 32%. As we have guided earlier, we have seen a significant increase in operating expenses as we expand the R&D activities with a broader clinical development program in particular. Looking at the quarter, in particular the fourth quarter 2021, we saw total operating expenses of NOK 51 million, and this compares to NOK 26 million, the fourth quarter of 2020. If you look at the key cost components, start out with the payroll expenses. We saw somewhat higher payroll expenses in 2021 compared to the full year 2020, NOK 62 million compared to NOK 51 million.
It's partly driven by two, three more FTEs, but also driven by higher share option costs as the share price has developed positively during the year. For the fourth quarter specifically, there's also a slight increase due to increased staff, but here we had an effect with a reversal of some of these share option costs, as the share price fell somewhat towards the end of the year. That reversal actually implies that the final cost decreased slightly Q4 2021 compared to the previous year. The main cost driver is of course the R&D expenses, and we saw a significant increase here, from 2020 of NOK 61 million up to NOK 88 million in 2021.
The reason is of course that we have initiated DOVACC and FOCUS in this period, and also we have further progressed the INITIUM, NIPU, and TENDU trials with more patients involved. We have increased the investments in CMC and some other R&D activities. When it comes to other operating expenses, there is just a slight increase from 2020. The total cash held by the end of the fourth quarter amounted to NOK 574 million. On the next slide, we're just showing the operating cash flow quarter by quarter. We see that the negative operating cash flows, which here excludes the public grants, have increased every quarter during 2021, which is in accordance with what we have guided during the year.
As mentioned, this is driven by the increased R&D activities, the increased amount of clinical development activities. Going forward, we expect this cost level to increase significantly as we further progress the clinical development program. On the next slide, we just show for information the breakdown of the key financials on a quarterly basis as support for analytical activities. With that, I will move to the next slide on the news flow and leave the word back to Carlos. Jens, so
When you talk about what's coming next, so as you see there, again, very successful quarter, but let's talk about the future. In 2022, we are gonna have further announcements in terms of data. During the first half of the year, as I mentioned, we expect to tell you when the first patient in the LUNGVAC study is gonna be enrolled. In the third quarter, we are gonna have an update on primarily overall survival for the second cohort in the melanoma study in combination with pembrolizumab. This is the two-year overall survival update. In the fourth quarter, the three-year overall survival update for the first cohort.
Again, very important data, because this will show really if, you know, we have the continuing benefit in terms of extending survival for these patients when we add UV1 to the treatment. Also towards the fourth quarter, we will have the final safety data on TENDU. In 2023, of course, very important period, during the first half, as communicated, we expect to release the top line results for both INITIUM and NIPU studies. Then, you know, we will provide you an update on when to expect the top line results for DOVACC, FOCUS, and LUNGVAC.
You know, we are also going to continue to look to present some of the data at medical conferences and also continue to put out publications in medical journals. Both of these activities are extremely important to raise awareness among not only the scientific and medical community but also to potential partners. We will also continue the dialogue with the pharma and keeping them up to date in terms of what the developments in our program. If we move to the next slide and just to wrap it up, repeating a bit what we already closed, but just as key takeaways. We have had a good clinical progress.
We had increased patient enrollment rate, particularly in INITIUM and NIPU, despite the challenges from the COVID-19. As a company, I'm very thankful to the team, very dedicated to make this happen. Of course, with a very strong commitment from the investigators and the patients, you know. It has helped that we have been in very frequent contact with all these investigators, and also has helped the fact that we have had quite good data so far in really supporting the interest from patients also to participate. The new study in non-small cell lung cancer is a further extension of our already broad phase II program. We have now five indications, different combinations.
When concluded, we'll have more than 650 patients enrolled in these studies, close to 100 hospitals in approximately 15 countries. This is quite an ambitious program, but also the result of the dedication of a team. You know, as a company, we are 26 people, so it's what we consider a great achievement that we can have such an extensive program in place. This is also important for you know, for us as a company, but also for our shareholders because really it spreads the risk and by having 5 indications, you know, we have multiple shots at goal as we use the expression.
The fact that we continue to have further encouraging results in the phase I study in malignant melanoma in combination with pembrolizumab is again very important for us and in a way, you know, supported together with the ipilimumab study, the grant of the Fast Track and the Orphan Drug Designations by the FDA. As you know, the TET technology is very innovative with a lot of potential, has a strong adjuvant technology that is basically a component needed in all vaccines, regardless of the type of mechanism used for these vaccines.
A lot of potential for this technology and of course important that we, the first study, as Jens mentioned in prostate cancer, is running because will be important to give us indications in terms of safety, dosing, immune activation to really support the continued developing of the TET platform and derive different products from there. All this is, of course, with the support from our existing shareholders that really had a strong participation in the very successful capital raise, really, you know, with a runway that takes us to the first part of 2024, allows the company and all of our colleagues to focus on the business and really it taking us this runway over the top line results of the first four phase II studies.
You know, LUNGVAC, of course, is one recent, but we will have, through this runway, data on INITIUM, NIPU, FOCUS, and DOVACC. Very, very good for a company to be so strongly financed and runway. With this, I want to thank you for your attention, and we will open the floor now for a Q&A. Thank you.
Thank you.
We'll open the floor now for a Q&A. Thank you.
Okay. I have received some questions. The first one is related to the patient involvement. Why INITIUM and NIPU trials are showing very strong involvement and DOVACC and FOCUS even on some slower start? What are your expectations to the patient involvement and DOVACC and FOCUS going forward?
Yeah, maybe I can address that. Yeah. As Jens mentioned and as Jens mentioned, the INITIUM study started enrolling patients in June 2020. Although we had some centers quite early in INITIUM and NIPU being activated only towards the end of 2021, you know, we didn't see an uptick for both the DOVACC, the FOCUS study, have started later. It was quite recent.
As Jens mentioned, we are in the process to open more and more centers. The numbers that you see are from a small number of centers in both studies. In DOVACC, we have only one. We expect now the number of centers will continue to go up in terms of the number of centers that are ready to enroll patients that we see picked up in the enrollment of patients in these studies. You know, FOCUS continues to enroll and DOVACC we expect now because the NSGO organization is very professionally organized to run gynecological oncology trials. We expect that now as these centers continue to be activated that the enrollment will
Carlos.
Yeah.
I get the message now that the sound is terrible. I think we need to ask for technical support if there is something to do about that before we continue talking. I will be grateful if someone listening could send me some way if the sound is better.
Okay. I will just talk to check that.
Yeah, that's fine.
You know, when I'm talking, if you maybe could, you know, just to make sure that that improves. Let's try again. I will be brief this time. If you can mute, Hans. Okay. Let's see if we can do this again. Apologies for the technical hiccups. Both INITIUM and NIPU studies are enrolling in centers. These studies are enrolling in 2020. We still have centers that are going to be activated and being included as recently as the fourth quarter. Both of them, DOVACC, are more recent studies. Both of them are in the process of activating and enrolling the centers that are going to enroll patients.
It's natural that the centers that are going to enroll patients is happening slower during this period of time. We will expect that the enrollment will be picked up and, you know, from now on. I don't know if the sound has improved.
I get the message that it did not improve, unfortunately.
You know, I hate that we have to repeat this, but let's see if, you know, I mute myself and Jens can repeat again, and let's try to do it the last time and see if this works. Jens, do you mind, please?
Thank you, Carlos. I hope the sound is okay now. If I also discuss regarding the inclusion of patients in the DOVACC and FOCUS trials. These two trials started at a later time point than the INITIUM and the NIPU trial. In the INITIUM and NIPU trial, all the centers are now open. As we have stated in earlier presentations, it seems like the activation of centers is a thing that goes a bit slower during the pandemic. As you have seen from the inclusion numbers today, it seems like when the sites are open, things improve. We are in the start phase of opening these studies. There are centers open in both the NIPU and the DOVACC trial.
Over these months, we are activating more and more hospitals and expect that the inclusion of patients will increase per month over the next period of time.
Thank you, Jens.
Hopefully that worked better.
Let's see if not. New questions, Jens?
Yeah. I guess the report is that the sound is better now, so we apologize for those technical challenges. Well, there seems to be a muting challenge. It helps when you mute. I believe Carlos and I muted. Let me see what the latest report is here. Sorry for this. There is this delay I believe, so that we need to be patient with the response from the audience. At least we need to ensure that everyone who is not talking needs to mute. That's for sure. If when I ask the question now, could the rest of you please mute and we try to continue. Okay. We have got a couple of questions on statistics.
I will try to sort of merge two questions that are quite similar. The company has previously stated that the readout of INITIUM will happen when 70 PFS events are reached. Are the statistics similar as in the NIPU trial with hazard ratio of 0.6, one-sided alpha of 0.1, and power of 0.8? And, a follow-up question to that, does this mean that the primary endpoint in INITIUM is 41 events in the control arm and 29 events in the experimental arm? Jens, please.
Thank you. First I would like to state that since these are randomized phase II trials that we have been discussing with the different authorities, the statistics in all the trials are as agreed with the FDA and different authorities in Europe. Why are they interested in the statistics? Well, one of the most important things for the authorities is to protect the patients. If you would like to start a clinical trial to test new drugs like the UV1, it's very important that the study has such a design that the study can answer the questions raised. We are confident then that the statistics in these trials are beneficial in such a sense.
The group behind the NIPU trial has earlier presented the statistics from the NIPU trial. In general, we can say that for all the endpoint-driven trials we are part of or sponsoring, the statistics is somewhat the same. That means that we are waiting for endpoints to occur, a predefined number of endpoints. The hazard ratio alpha and the power of the trials are almost similar in the trials. For these endpoint-driven trials, what you do is that you take results from earlier trials and try to understand what drug that are in the both arms. For example, INITIUM trial with nivolumab and ipilimumab, and try to understand what is the median PFS in earlier trials.
You use that number, together with other assumptions to calculate, how many patients to include in the trial, over which time the patients should be included, and how many endpoints you need before you can close the database. When there is different things occurring in the trial, for example, then that the inclusion of patients takes somewhat longer, that will not affect the statistics in such design. So that we now have reported a somewhat delay in the report of INITIUM and NIPU trial will not affect the statistics in the trial. Was it the second part of the question should I also address? If you could read the last part of the question once more.
You should mute, Jens, to be sure that the sound is okay. Specifically a follow-up to the first, does this mean that the primary endpoint in INITIUM is 41 events in the control arm and 29 events in the experimental arm?
The statistics we are testing a so-called Kaplan-Meier plot. We are following the patients in the two different arms, and endpoints will occur in the two different arms, hopefully, at a different rate. When in total, around 70 endpoints is reached in these trials, we are closing the database, and then we are looking at how many patients will be in the intervention arm with an endpoint, and how many patients will be in the control arm with an endpoint. We have, based on discussions with authorities and external experts, the doctors, in a way agreed what is a good clinical benefit for the UV1 vaccine.
The sign of the statistics in the studies are made so that if the study is positive, it's a clinically relevant achievement on top of standard of care. The number can be hopefully below the line we have drawn, but what the number will be is impossible to say. It could be far better than we have expected, or it could be slightly positive or hopefully not a positive results. When we have the results, and if the trial is positive, we have discussed the line, and that line will give clinically interesting results that will benefit patients moving forward.
Okay, if you all could please stay muted now when I ask the next question. I have been asked by the audience to repeat the first question and the response to that, 'cause I think it may have been very difficult to hear that. I'll repeat that first question again. While the INITIUM and NIPU trials are showing very strong enrollment, DOVACC and FOCUS seem to have a somewhat slower start. What are your expectations to the patient enrollment in DOVACC and FOCUS going forward? And then I'll mute.
Okay. Jens, why don't you take over so maybe this works now.
Thank you, Carlos. So first for the INITIUM and NIPU trial, just a few comments there. Remember that both the INITIUM and NIPU trial, they are like pivotal studies. They started to enroll patients after the start of the pandemic. All patients and all centers have been activated under the pandemic. We have gained some interesting learnings from that, and it seems like opening of centers is more tricky than inclusion of patients. That might be due because patients are on home office. It's less face-to-face communication, et cetera. Activation of centers have gone a little bit slower than expected, as Carlos said, but all centers are open in the INITIUM and NIPU trial.
The pandemic is still there, and we have opened even more trials during the pandemic, like the DOVACC and NIPU trial. Over the period since first inclusion of patients, we are continuing to opening hospitals, and that is the main thing we are working with these months. We expect that enrollment in the DOVACC trial and the NIPU trial will increase over the next months where more hospitals are opened, and also hopefully we can dream for another scenario that the pandemic will in a way disappear or be less involved in our trials over the next period, so that inclusion can increase even further. We will, as Carlos stated, have an update on the readout from these trials at Q4 report in 2022.
Okay. Thanks, Jens. If you could please mute again. Now, there is one financially related question. You say costs are expected to increase significantly. Do you have a breakdown or estimated expenses per quarter going forward through 2023? When we have been guiding on costs, we have not and we do not plan to share details or on projects or quarters. We do provide continuous guidance on financial runway.
The nature of these large R&D trials that we're running is that it's fairly easy to estimate the total costs, but it's more challenging to estimate the exact timing quarter by quarter, 'cause it depends on key drivers like patient enrollment numbers, and other studies somewhat less easy to control fully. We do not want to share that level of detail. Of course, internally we have this all lined out as part of the planning, but we don't think it's appropriate to share that level of detail externally. We provide a direction, a guided direction on the costs and the financial runway. Thank you. We have. Let me just check if there are new questions coming in. No.
We have one last question, it seems. With positive results from INITIUM, what are your expected next steps? I guess this goes to Carlos.
Thank you. Well, assuming INITIUM positive results, as we have mentioned, we basically as a company have been also developing in addition to the data, other areas of the business to support the product going forward. Like for instance, you know, working on a commercial process of manufacturing, very important. The next step after the data from INITIUM would be depending on how strong is that data, to discuss with the authorities, because that's part of the normal regulatory process. During those discussions, if the data is very positive, we can discuss with the authorities the potential for an accelerated approval. Then of course having to do confirmatory studies. That is a normal process.
Talking with the authorities, defining then the next step that will be from the perspective development to run a phase III study. This is important that we do this as a company, because this is also important when we, after we get the data, and assuming it's positive, we start talking with potential partners, for them to pick up on the continue developing of UV1. We believe this is, this is important to emphasize because, as a company we need to be prepared to do it by ourselves, you know, and because whatever we do will be of value to partnering discussions. As stated several times, we believe that a commercial partner with a stronger commercial financial power can really maximize the value of UV1 moving forward.
Because we are putting in place all the data that a partner could move, not only with one, but two, three, several pivotal studies, or what we call approval regulatory studies, after this data is out. You know, in short then we will continue, put all the pieces of data together, we discuss with the authorities, not only in terms of what will be the design, but also the potential for accelerated approval. This is what we have to do. In parallel, based and supported by this data, we will activate even more the discussions with potential partners for, you know, enter into a licensing agreement.
Thank you, Carlos. There are no further questions.
Okay. If there are no further questions, we want to thank you all for your time, and again apologize for some of the initial technical challenges during the Q&A. Of course, please feel free to reach out if any other question remains, and you want to discuss it. With this I want to thank not only Hans and Jens that are here, you know, for this webcast, but also thank all of our colleagues at Ultimovacs for their dedication in making this very successful quarantine year happen.
I also thank all the physicians that are treating the cancer patients for their commitment, and also of course the support of all of our shareholders that allow us to really dedicate our time and energy and efforts in finding new treatment alternatives for cancer patients, what is really our ultimate goal. Thank you everybody, and have a good rest of the day.