Good afternoon, everybody, welcome to Ultimovacs first quarter 2023 results. As usually, I have with me Jens Bjørheim, our chief medical officer, and Hans Vassgård Eid, our chief financial officer. You have the opportunity to ask questions, send questions during the presentation, and we add it to the ones that we already received, and we will try to answer as many as possible after the presentation. We've moved to the next slide. you know, I have to show you the disclaimer. In the next slide for, just to take in consideration that some people may not be so familiar with Ultimovacs, I'll just give a quick introduction before moving specific to the quarterly results.
Ultimovacs is a clinical stage biotech company, and we are developing a universal and off-the-shelf cancer vaccine that in a broad clinical program has the goal of showing that UV1 can be used in multiple cancer types and in combination with different classes of drugs. We target an enzyme that is expressed in 85%-90% of cancers throughout all the disease stages. The vaccine is easy to use, intradermal injection, and as I mentioned, has the potential to be used in multiple cancer types. The team has been doing a great job together with the investigators in developing a vast clinical program. We have currently 1 phase II and 5 phase II trials ongoing, and we also have multiple phase I in long-term follow-up. As a matter of fact, we have studies being followed up for now the 10 years.
In this study, so far we're showing a very good safety profile, efficacy signals that Jens will share some of those with you, and also what we say is immune response durability. We still find T-cells, immune cells in circulation recognizing telomerase, in patients that were vaccinated seven and eight years ago. As you will see, we are in a very exciting period for the company with a very near-term key inflection points, as we will have readouts from three of our five randomized comparative phase II studies. We have a strong external validation, not only by receiving the Fast Track Designation and Orphan Drug Designation in metastatic melanoma by the FDA, but also the fact that we work together in joint projects with key oncology centers and also two large pharma companies.
w to the next slide, and we talk about the quarter specifically. Again, you know, a very good quarter, where the team has been primarily focusing for the multiple catalyst events that are approaching the company over the next months as our clinical program progresses. As you know, we are a rigorous data-driven company with a strategy to basically bring as fast to the market UV1 and into as many patients as possible. The cancer vaccine UV1 is, as I mentioned, investigating 5 randomized comparative phase II trials, different cancers at different disease stages, different tumor types, different biologies, and different treatment regimens. And we are enrolling now patients in Europe, the U.S., and Australia.
A very important and a great achievement by the team and the investigators, we have now more than 50% of the 670 patients that are included in our five phase randomized studies already enrolled. Very, very important milestone for us. Jens will give you a little bit more detail about the enrollment, but we completed a NIPU enrollment in January 2023, and we continue to give guidance to have the readouts available now in the second quarter 2023. The enrollment in INITIUM was completed a year ago, and we have now extended the timelines and the expected readouts to the second half of 2023 because these patients are responding to treatment and taking longer to progress or die.
We continue on track in the enrollment of FOCUS, our head and neck cancer. We have now more than 80% of the patients enrolled, and we expect a readout in the first half of 2024. The DOVACC study in ovarian cancer and the LUNGVAC in lung cancer are at early stage but also now picking up in terms of enrollment, and we expect readouts in the second half of 2024 and also in 2025. We are very pleased to receive IP protection now, the new combination patent of UV1 with checkpoint inhibitors, now in Europe.
This is similar to the one we received last year in the US, and very importantly, extends the patent life to 2037 before additional extensions. We, as part of our strategy to strengthen as much as possible the patent portfolio for UV1 and for other products in Ultimovacs, very important. Despite some of these movements in terms of guideline, we continue to have an expected runway to meet 2024. This is very important because this runway takes us through 3 expected results in 3 phase II studies.
Very important to to be particularly in these, in these times, financed and with a good runway, as we hear in the market from both companies and investors that is quite a challenging time to to raise capital. We are very pleased that we are not only financed, but during this period, we are gonna have three potential key inflection points with the results of three of our studies. If we move to the next slide, I will give now the word to Jens, and we'll come back later on. Jens, please go ahead.
Thank you so much, Carlos. Please proceed to the next slide. First, a short update on the inclusion numbers in the different trials. As Carlos mentioned, the patients are fully enrolled in the INITIUM trial in malignant melanoma and also in the pleural mesothelioma trial. For the FOCUS trial, 61% of those 75 patients are enrolled as of now. That is compared to 50 at Q4 report. For the DOVACC and the LUNGVAC trials, these two trials are early on still. Inclusion is 24 patients in the DOVACC trial and 7 patients in the LUNGVAC trial. For the TENDU trial, 12 patients were enrolled earlier, and there's no new information on this trial at this presentation.
If you go to the next slide, this slide shows the clinical program we are conducting in Ultimovacs. A few considerations around this. As you know, the lead indication and our sponsored indication is in patients with malignant melanoma. We have conducted 2 phase I trials that are completed and reported, and we have a phase II trial, which has also completed recruitment and will report estimated as second half of this year. Over the last years, it has been a lot of interest from academic groups and also other pharma to involve UV1 in different clinical trials. As you know, we are participating in 4 such trials in mesothelioma, head and neck, ovarian cancer, and non-small cell lung cancer. Why are we present in so many different trials? I have a few comments on this.
First, and for these indications, it's important to understand that these are indications where almost all patients are expected to express telomerase. In these indications, you do not need a diagnostic tool upfront to identify the patients to include them in the studies. The other thing that we believe is important in trials with vaccines is to combine with the checkpoint inhibitors. In all these indications, there are either good evidence or standard of care treatment with checkpoint inhibitors. Over the next few slides, I will discuss these two things, the telomerase part and also the efficacy of the checkpoint inhibitors in the different indications. First, for the telomerase. Telomerase is an enzyme that is allowing the cells to divide, at least in theory, forever.
There's a group of different aspects around the cancer cells that need to be in place for a cell to be defined as a cancer cell. It needs a strategy for eternal cell division, for example. In 85% to 90% of cancers, expression of telomerase is there to fulfill that demand. The hallmarks of cancer, they are often essential, or they are pre-requisited. It's something that you need to have in place to move a cell from a normal cell into a cancer cell. The telomerase expression will be there in all parts of the tumor from the early stages of cancer and also in all parts of the tumor, both in the primary tumor and in the metastasis. The tumor cannot turn off the telomerase because then the ability to have eternal cell division will disappear.
We know that our target is present in the patients in our indications. As you know, from the all the studies with checkpoint inhibitors over the last decades, what they actually do is that they remove a part of the resistance towards the immune system so that the preexisting immune system can kill off the cancer. If you look at the next slide, we have taken some data from the registration trials for malignant melanoma, mesothelioma, head and neck cancer, and non-small cell lung cancer, as you can see in the table to the right.
The black triangles represent the median PFS in these 4 different indications, the red columns the response rate, and the green columns, the complete response. As you can see, if you use different, if you use immune therapy in the form of checkpoint inhibitors in these different indications, you can see different answers in the different patient populations. There are different biology in the different cancers, not only in the indications, but also between each individual with the disease. As I said on the previous slides, in our clinical trials, we have 2 things that need to be in place. The telomerase should be expressed in the tumor, and there should be checkpoint inhibitors, and that is a standard of care or have proven to have good signals in larger trials.
Our question is actually what happens if you add UV1 to the current standard of care in these indications? As you can see, even if the response rate is 50% in melanoma, you only see a complete response rate around 10%, and for other indications it might be worse. There's a lot of patients that have an unmet medical need. How the vaccine is working in these indications is what we like to know. What will the efficacy of the vaccine on top of checkpoint inhibitors be? Will it be that more patients stay in a partial or complete response? Will it be that PFS is expanded in all patients or in groups of patients?
Will it eventually lead to extended survival for the patients, which is the ultimate goal and gold standard endpoint for these patients. By having five different indications in randomized phase II, we find ourselves in a very good position because the different biology will help us to understand the tentative mode of actions of our vaccine in different biology and with different checkpoint inhibitors moving forward. This will be very valuable information for us moving into phase III programs in different indications. Just to repeat some of the signals that we have seen earlier on. On the next slide here, you can see the PFS and overall survival in our trial in malignant melanoma, where we combined with pembrolizumab.
We had a readout of the median PFS at 18.9 months and 1 and 2 years overall survival was 86% and 73% in this trial. Further on, if you look at these trials individually, you can see that on the next slide, in this spider plot, each line is represent 1 patient and each of the box it is representing an image of that patient. You can see number of weeks at the X-axis and percentage change in the tumor lesion on the Y-axis. All the green lines represent patients that are in so-called partial response, meaning more than 30% of the tumor is gone or in complete response, meaning that all of the tumor is gone.
We followed these patients for 2 years. What we saw was after 1 year, 24 of the patients that were in a partial or complete response were still in that condition after 1 year. On the next slide, you can see the same patients in a waterfall plot. Here, each patient is presented by a column. The stage of the disease for each patient is annotated above or below the columns. Also there is some information on different biomarkers that are associated with good or not that good response to immune therapy like TMB, tumor mutational burden, LDH and PD-L1 status. As you remember in this study, we actually saw that 1/3 of the patients had a complete response.
When we looked at the group of patients that had PD-L1 negative status, which are linked to not that great response rates if you use checkpoint inhibitors alone, we actually did see the same response rate, both when it comes to complete responses and also for responses as such. Just for information, we are added the information on this from the KEYNOTE-006 trial below the waterfall plot, where you can see to the right down part that the complete response in those that were PD-L1 negative were 6% and the overall response rate was 24% versus response rate and complete response in the total population being between 34% and 42% and between 5% and 14%.
There are signals here that both in this small trial of course with 30 patients, but in this small trial, we did see that patients that were PD-L1 negative responded the same way as the whole group. That is something that we find very interesting moving forward. Another thing is that we actually saw quite a few complete responders. We did see more complete responders than partial responders, which is also uncommon to see in trials with checkpoint inhibitor treatment alone. These signals of efficacy, how they will translate in the phase II trials that are starting to read out would be very interesting, and we are very happy that we are in different biologies that can maybe unveil these mechanisms better in one form of biology than another form of biology. Moving on to the next slide.
The first, or the sponsor trial for us, the INITIUM trial in metastatic or advanced and metastatic malignant melanoma, was fully enrolled as of July 2022. Inclusion of patients were conducted in the U.S., U.K., Belgium and Norway. This is a so-called endpoint-driven study, meaning that based on historical data and the statistics and the inclusion rate in the study, we wait for 70 endpoints to occur. As we informed in end April, those 70 endpoints had not occurred as of late April, we expect readout of the trial now in second half of 2023. That we wait for a longer time for the 70 endpoints to occur is positive for patients, it means that they progress or die at slower rate than expected.
We also have a small single arm study which is connected to Initium. It's not part of the Initium trial. It will not be part of the primary endpoint readout of Initium. It's a cohort of patients and with the same inclusion and exclusion criterias, where we will have a lot more information about each of the patient. There will be liquid and solid biopsies at different time points throughout the treatment of these patients. For us, and this is very information to get, so that we can correlate R&D findings within the tissue of these patients with the clinical efficacy in patients. This is both information that is important for later filing, and it's also information that is important for us, moving forward and in selection of design of future trials.
After we have reached 70 endpoints in the INITIUM trial, the database for PFS will be locked, but all patients will still be followed up for overall survival over the next years. Even if, and that goes for all the patients included in the study. You move on to the next slide. Some comments about the malignant pleural mesothelioma, which is the NIPU trial, which we expect to have a readout now in 2Q of this year. You know, mesothelioma is an aggressive cancer with high mortality, and there are few therapeutic options. When we started, together with the OUS and Bristol Myers, the NIPU trial, there were no established second line treatment in this indication.
While we were starting up the trial and had started to include patients, the same autumn, actually FDA approved Ipi-Nivo as a first line treatment in this indication. This is somewhat good news for the patients. It improves the overall survival somewhat, with from 14 to 18 months in these patients. Of course there is still room for improvement, there's mortality in this trial. 16% of the patients are without progression at 2 years, and 41% of the patients are alive after 2 years. Moving on to the next slide. The NIPU trial is expected, as I said, to have a readout this second quarter. It's sponsored by Oslo University Hospital.
It's also an endpoint-driven trial, meaning that we are waiting for a predefined number of endpoints to occur for the primary endpoint is closed. The study started to recruit patients back in June 2020 and full accrual in January this year. Yes. Over to the next slide. I guess this was the last one for me, so I give the word now to Hans.
Thank you, Jens.
Yes. Thank you.
We'll give a brief financial update. By the end of the 1st quarter of this year, we had a total cash holding of NOK 406 million, roughly $39 million. That is down from NOK 425 million 1 quarter back. We do maintain the guiding that the expected financial runway is until mid-2024. The extended time to read out in the INITIUM trial is not expected to have any significant impact on the financial runway. Of course, there are some costs associated with the extension, we see no need for changing the guidance. Some key numbers.
The operating result, the EBIT, in the first quarter was negative NOK 51 million, and the profit before tax in the quarter was negative NOK 34 million. Some high-level comments to the operating expenses. Looking at the payroll expenses, the underlying salary expenses are fairly stable, but there are some quarterly variations in the total personnel expenses, which is due to the cost associated with the share option program, largely driven by the share price development. When it comes to the main cost driver, R&D expenses and IPR expenses, that was significantly higher this quarter than the similar quarter last year, but lower in the first quarter this year compared to the third and fourth quarter last year.
On cost guidance, going forward, we expect that the operating expenses should increase further compared to the 2022 level and also the level we had this quarter. There will continue to be quarterly variations. The expected increase is driven by further progress in the phase II trials, CMC development costs, that is manufacturing-related, and other R&D activities. I think it's maybe important to emphasize that the increased cost level or the next quarters that is related to defined projects. We do maintain a lean business model. We have only 26 employees, running the significant operation we have as of today. We are not planning to make any significant increases in the fixed cost base.
We are not making specific investments in infrastructure and such things, the lean business model we expect to maintain. This means that when the defined ongoing projects are completed, future burn rate will then be a function of what new projects we initiate, that will largely depend on the outcome of the phase II trials. On the next slide we have some more details. I would just like to point a couple of points here. We, when it comes to personnel expenses, payroll expenses, the share option costs constituted NOK 6 million in the last quarter, and that is NOK 8 million higher than the same period the previous year. There is a significant increase driven by development in the share price. To a large extent, these costs are non-cash costs.
This quarter, we had a positive contribution from financial items, with a net contribution of NOK 16 million-17 million. That is partly driven by interest rate income and not least driven by net foreign exchange gain related to our hedging positions, where we have some positions hedging the expected expenses in euros. While the total operating expenses were minus NOK 50 million-51 million, the total loss was reduced to NOK 34 million due to these financial items. On the next 2 slides, we have the regular cash operating cash flow illustration. Also on slide 20 we have the breakdown of the quarterly financials. I'm not going to go into detail on that, but they are there for reference.
With that, we can move on to slide 21, and I'll give the word back to Carlos.
Thanks, Jens, and thanks, Hans. If we move to the next slide, let's talk about what's coming next. As already mentioned several times, exciting period for the company. Clearly, we still expect this second quarter, the results from the NIPU trial. This is gonna trigger, if positive, a series of activities within the company that will be similar to the other studies. These activities are linked to different groups. You know, we will be meeting with the regulatory authorities as expected. If the data is positive, we will be discussing with them the next stage of development, the possibility of having, for instance, an accelerated approval, filing for a Breakthrough Designation, Orphan Drug Designation.
A lot of regulatory activities, supported hopefully by positive data. Also in parallel, you know, we will be continuing more actively discussing the data with pharma companies that are potential strategic partners. As you know, we are in regular contact with these pharma companies. And of course, they are also like us and a lot of other people waiting for the data. Again, if we have positive data as we hope, you know, this will also trigger a series of activities in discussing the data with these companies and discussing strategic options for a potential licensing of UV1 to these pharmas. We are prepared, as you know, as a company to continue by ourselves. We have all the plans in place and the investments, you know, ongoing.
We continue to believe that a strategic partner will be able, with different resources, including financial, to move into a very broad phase III program, and in reality, hopefully bring UV1 faster to the market and to more cancer patients, you know? That is ultimately our goal. As a company, you know, we want to be able that, supported by positive data, that UV1 is as fast as possible available to as many cancer patients as possible. That's our goal, this is also why, as a company, you know, we will start on the back of the data from NIPU, proceeding with all these activities related to mesothelioma while we continue to wait for results in the other indications. The next one, you know, as we guided is INITIUM.
Not the next slide, sorry. The next indication is INITIUM that, as Jens very well explained, is now expected in the second half of 2023. We also in the first half of 2024, we expect the results from the FOCUS study in head and neck cancer. You saw that, you know, enrollment continues at a very good pace. Of course comes DOVACC in ovarian cancer and LUNGVAC. As a company, we have multiple studies, as we continue to emphasize all of them randomized and comparative.
I want to emphasize this because as we regularly meet with the specialist investors and with pharma companies, if you don't have comparative data, you know, comparative trials with data from these studies available, it's gonna be very difficult to gain any attention from both pharma companies and the specialist investors. It's a big effort for the company and the team and the investigators, but it's very valuable that all of our studies are randomized comparative. A very busy period of time. You know, we hopefully we will get positive data in as many as possible. As Jens explained, you know, all these types of cancer and these patients have different biologies, different behaviors. The checkpoint inhibitors are not, you know, have efficacy in all of them, and the efficacy level is different between indications.
Ultimately, as Jens mentioned, our goal is can we improve the number of patients that have a response to checkpoint inhibitors and improve even that response. I think that, you know, we will also come then in the second half of this year, we'll be able to give you a little bit more updates on the, on the TET platform, including the TENDU study. I mentioned that several times. We have a series of non-clinical activities, CMC activities, and of course the TENDU trial. We expect to give you a more full update on the technology and the plans in the second half of this year. This is probably, as in you see in the next slide, the best time for UV1 to be having data from these studies.
d of course we hope that it's positive, but this is extremely important for the company that now the attention to cancer vaccine has been really increasing on the back of the deal that Moderna did with Merck end of last year, the recent data from Moderna in adjuvant melanoma patients, you know, really has changed the tone and the interest for cancer vaccines. If we have positive data, this will be a lot of attention to the company, to the data, as we will be, you know, the first company with a universal vaccine and with randomized data showing that the cancer vaccine has a role in treating cancer patients.
You know, this is important, as I mentioned, because as you see in the next slide, we have quite a very competitive profile when you look at other cancer vaccines, including the Moderna vaccine that, as you know, is a individualized vaccine. Why do we say that UV1 has this potential, and why is a universal vaccine? Well, first, because, you know, is an off-the-shelf product ready to be administered when needed. You don't need to do any screening of patients before you treat these patients. You can treat. UV1 is ready to be administered being in the U.S., in Europe, South America, Asia, Africa. The vaccine is the same. It doesn't matter your gender, your race, you will always use UV1, and it's off the shelf. Another very important factor is that it's easy to administer.
These are 8 intradermal injections, so the fact that you don't need to do any biopsies to prepare the vaccine, you don't need to inject the tumor or the metastasis. The fact that this sits in the normal fridge and ready to be administered makes it possible to be used regardless of where the patients are. One of the topics that is being now discussed more and more among pharm and among physicians is access, patient access, not only in terms of pricing, but primarily, you know, that a cancer patient can be treated even if they are not close to a very specialized center, and UV1 allows for that. Also, it helps that it's not a complex production process. You know, It's a low-cost production process.
You know, we as you know, was important investment from the company, to have by when we have the data that we will have a commercial, a product manufactured in the commercial process. This is extremely important when we or the strategic partner moves to phase III, but also will be very important if the data supports, for instance, the discussion with the authorities for accelerated approval. You know, the fact that it's simple logistics, it's the normal fridge and no complex infrastructure distribution required. really gives UV1 a very competitive profile. makes it really this universal concept that in addition to the fact that we can be used in hopefully multiple cancer types. Not all of them, of course, we don't expect that.
As you know, including the checkpoint inhibitors, they cannot be used in all cancers. We hope in a broad number of cancers and the fact that the target is expressed in 85%-90% of cancers. Really supports this concept that we want to this goal that show that UV1 has universal profile and really, hopefully, a broad applicability. If we move to the next slide and to talk about, you know, how we hope to get closer to our shareholders. We had an event in Oslo, I know was the first one. Probably our shareholders are still getting used to it, as was mentioned, we are a small team, very busy, we still try to build opportunities among this very busy schedule to meet with our shareholders.
The next opportunity will be for investors, shareholders, interested people that want to meet with us in Bergen. The date is at the moment planned for June 20th. Of course, we'll be looking for other locations and other dates to continue have the opportunity for our investors and shareholders to meet the team that is delivering on these results. You know, in the next slide, and before we move to the Q&A, I think just want to summarize the first quarter. Again, a very good quarter for Ultimovacs. We completed enrollment in NIPU in January. We heavily discussed, patients are, you know, responding positively to treatment and taking longer to progress. We had to move the readouts from the first to the second half.
We have in the next months expecting several key value inflection points with NIPU now in the second quarter, INITIUM the second half, and FOCUS in the first half of 2024. All these while we still have a cash position. We also see that the interest for cancer vaccines has been really increasing enormously, not only from the news, but also when we meet with pharma companies and particularly with specialist investors. They are very pleased by the fact that all of our studies are comparative studies.
They say that otherwise they would not be talking to us, and they really are genuinely hoping that we have positive data because they really see this will be an important addition to the treatment alternatives for cancer patients that need as many alternatives as possible. We continue to deliver on our strategy to strengthen the patent portfolio with the new patent granted in Europe and similar to the one that we have in the U.S. As mentioned, we have a financial runway still expected to meet 2024. You know, very exciting periods for, I'm sure for us, but also for you in this call. That is the expectation for the data. That potentially can be transformational for the company and most primarily to cancer patients.
With this, we want to thank you for your attention and time to the presentation, and we can move now to the Q&A. Hopefully, in addition to the questions that we have received so far, you have additional questions during the presentation, and we can move to those. I will ask Hans to take the lead there.
Yes. Thank you, Carlos. We have received several questions, so I will start with a couple of questions related to the INITIUM trial. How many events did you have in the INITIUM study by the time you delayed the results to the second half of this year? Does the delay have anything with longer cleaning time than you had expected?
Well, as you can imagine, you know, we cannot. We don't, we don't have the data, you know. We know that the postponement of the readouts to the second half is not due to that it takes to clean the data. We know that we don't have yet 70 events, and that's the only reason why we have to move the readout to the second half. We, you know, don't have the details about number of events. We know that we haven't reached the 70 events.
Okay. Another question. Can you list some theoretical possible reasons that the results in the control arm in INITIUM can be significantly better than in historical studies like CheckMate 067 and CheckMate 511? Another question related to that, we could add, could a pandemic influence enrollment in a way so that all patients in INITIUM are healthier than in the historical comparable trials?
Well, it's a very good question. You know, we'll ask for a lot of speculation. You know, as you know, as the company, we are science-driven. We, we communicate on facts. I think, you know, we have been very transparent in communicating that. You know, we publish all the data every quarter. We, we are transparent in saying how many patients are enrolled. We, we know that when we, Jens and the team designed the statistic plan for the study was based on the historical data in the study that were mentioned. We know that it's taking longer than than in the historical data. We don't really know why that is the case. You know, we will need to be speculating. You know, you can have multiple reasons.
Of course, can be because UV1 is having an impact, can be because the patient in the studies is different. The pandemic, the COVID pandemic, in reality, from the information that we get, is probably making it harder for patients to be treated. We know that a lot of patients got delayed in diagnosis and then in treatment because they didn't have access to hospitals. The important factor here is that again, one of the values of having a comparative studies is that, you know, these patients are randomized in through tables. You know, no one decides which patient goes to which group.
All the patients have to meet inclusion criteria and exclusion criteria that are very similar to the studies that were referred. If the COVID have an impact, you know, it will have an impact in all of the patients. We also mustn't forget that the INITIUM study, you know, about 50% of the patients were included in the U.S. in different hospital in different states, in 3 European countries. You know, the U.K., Belgium, and Norway. You know, these are 40 different centers, you know. The COVID reality and practice were all different in not only inside the countries but also from hospital to hospital. You know, it may be that the COVID have an impact. We cannot say that.
What we hear is more that, you know, patients were diagnosed and treated at later stages. Again, the beauty is that we will be able, when we receive the data, to see if these factors have any impact because we will have the data, and we can compare if the patient that were treated earlier in the pandemic have any different on the ones that were treated later, any difference between the centers. Most of all, we can compare if. Because these impacts should go randomly across the different groups. Ultimately, what we want to assess is, of course, if UV1 brought an improvement in the efficacy of the checkpoint inhibitors into these patients.
Okay. Thanks, Carlos. Another related question that you may partly have answered already. Regarding the INITIUM trial, if we hypothetically assume the case where both arms are doing better, do you see any risk for UV1 not reaching the expected statistical level of improvements versus the control due to control patients reaching a PFS harder to improve substantially?
Jens, do you wanna comment on that again?
Uh-
This will be a speculation but just a comment on the science. Yeah.
Yeah. With this design, with the endpoint-driven design, there will be the areas, you know, between the curve axis and x-axis, the ratio between those areas that define the hazard ratio in the trial. The form of these curves, how that will, what kind of endpoint that will lead to would be very hard to understand. I see your point with higher PFS in the control arm. If there is a positive effect of UV1, it will also likely take a longer time to read out the results because it will take longer time to get the 70 endpoints.
Okay. A last question related to the INITIUM. It's a, it's a bit long. When we hear our top-line results being pushed back, many investors often think this is to do with trial delays or issues with patient enrollment. However, this is quite the opposite for the INITIUM study, and a slight delay in expected timelines is because of highly encouraging trial observations. Could you explain why the guidance for trial readouts from INITIUM has changed and why this is in fact a positive result for patients in the study?
I think the question already covers the some of the points, and Jens also touched on this during the presentation. As he explained, you know, we stopped the study to analyze, and then of course, we'll continue following these patients for survival when 70 patients progress or die. We were expecting, anticipating based on historical data that those 70 events would have, you know, happen during the first half of 2023. You know, clearly, the patients are responding to the treatment, you know, although we don't know, you know, what is the difference between the groups.
It's very good for patients that it's taking them longer to progress or die and that is the only reason why we need to move the guidance to the second half because the time to reach the 70 events is taking longer than anticipated based on this. This is a very positive aspect. It's not because Jens, you know, we had problems in enrolling these patients. You know, we finished enrollment of these patients in June... July last year. You know, in a month time, we will have patients that have been on the study for 3 years. Enrollment happened really in a, what I would call even in a record time.
Patients are being followed. The only reason is that the patients are responding better than was anticipated based on historical data. No red flags. It's just the development of the study. It's positive that it's taking longer for patients to progress or die.
Just one general comment also. Since we have discussed today that we are in different indications where checkpoint inhibitors have different efficacy, and also that at this stage of vaccine development, we need to have further understanding of the mode of action. Of course, we have some ideas where the vaccine will have mode of action or the T-cells expanded by the vaccine. For us, it has been very important to capture the whole part of the curve where things happens with patients. As you know, even if we don't have a curve here right now, most of you will likely know that in the checkpoint inhibitor curves, there's a steep fall in the beginning and then a curve, and then the curve flattens out.
To really be able to capture all of that, it's important that you have this endpoint-driven design because you can then look at the curves at the different time points from start of treatment until everything slows down and the curve flattens. That is in contrast to landmark trials often where you decide a point where you want to check what the difference between the two arms are. Even if it's take longer, it will be of high value for the understanding of mode of action in different indications.
Okay, thanks. We have a few question related to the NIPU readout. I'll read three different questions which are quite similar. Having now reached 69 events in the NIPU study, may it be delayed to the second half for the NIPU trial as well? I'll read the second one. Given that you have defined data cleaning activities to last weeks to months, at what point would you change NIPU data guidance if you have not already received notice that 69 events have happened? I just also add the third one. Estimated readout from INITIUM was changed from the first to the second half of this year. Can estimated readout from NIPU also be changed to the second half?
Well, thanks for the questions, you know. As was already explained, the INITIUM is Ultimovacs's sponsor study, so we have a little bit more information, you know. For regarding NIPU, we have no reason so far, informed by the investigator that we should change the guidance. If that happens, we will inform the market. Currently, we still expect the NIPU results to come now in the second quarter of 2023.
Okay. Another question related to NIPU. What would constitute a successful result in the NIPU study, and what would you consider a good enough result with respect to median PFS and HR to get accelerated approval?
Jens, do you wanna start?
Well, you know, all these clinical trials, as you might know, you have a new hypothesis that both arms are working the same way. Based on previous data or what is expected in the clinic when it comes to efficacy, you decide how much different the results will be if you add a compound. For example, like the UV1 compound. In this trial, we have defined a hazard ratio of 0.6. When you do all these calculations, I'm not able to go through that, it ends up that if the hazard ratio in this trial is below 0.73, this trial will be a positive trial.
By positive trial, meaning that it means the pre-assumptions that P will be below 0.1, one-sided, which was the design suggested from our statisticians. That is a positive trial. That is something that will have results that, in a way support further development of the combination in this indication. Of course, you also need to take into consideration that the world is moving also elsewhere, you need also to place a study in a good and safe place, to put it that way, so you know that inclusion will be fulfilled and that you, in the end after phase III readout, don't only have a positive trial, but also a clinical relevant trial, so the drug and combination are used.
When it comes to, how good must the results be for this to be accelerated approval, this is a discussion between regulatory authorities and the companies. To speculate about that will be both very difficult and we do not know the answer to that.
No-
Okay
thanks, Jens. I think just to, just to, you know, pass the comments. You know, again, this is for the authority to decide if the data is strong enough for an accelerated approval. Also as Jens mentioned, you know, in mesothelioma there's not a lot of treatment alternatives, and in reality not in many studies to guide us. You know, we... the expectation is because this is a very high in medical need there to... any improvement will be valid for, valuable for these patients. Hans, next question.
Yeah. We have 3 minutes left, I hope we can cover 2 questions at the end. First, with the positive results coming from personalized vaccines, how do you think about the competitive position of UV1 in the emerging landscape of cancer vaccines?
Yeah, this is a very important question. Hopefully I covered this during the presentation. You know, what is called personalized vaccines, in reality even the companies are now changing the nomenclature to more individualized vaccines, meaning that you go patient by patient. In reality, UV1 is to start a universal vaccine with all the benefits that I mentioned. After you inject UV1 in the patients, you get a personalized response, you know, that is different from patient to patient. I think we, you know, we don't, honestly, we don't look at individualized vaccines as competitors for UV1, because the fact that, you know, there's very important facts that we don't need to do biopsies.
The cancer cells are difficult to mutate out of telomerase, and the easy manufacture, accessibility to patients to be treated in everywhere and not just close to specialized centers. We see the value of individualized vaccines as we see in any treatment that brings a benefit to patients, but we don't see them as direct competitors to UV1.
Thanks, Carlos.
The last question, Hans.
I think we have time for one last question. If positive results are generated from initial NIPU, how would you envision the path forward for Ultimovacs?
Well, you know, I think I also covered that, but I would like to again repeat that as a company, we are prepared and our plans is assuming success. It's that's how we need to prepare. We are prepared to move to phase III in mesothelioma and in melanoma. Of course, you know, having to get additional financing, we don't see that as a problem or as a challenge in the back of positive data. What we believe is that on the back of positive data, the discussions with potential partners will necessarily accelerate. That's how we see the moving forward.
Increasing the contacts with the authorities, accelerating discussions with potential partners. Also of course raise the profile and awareness of Ultimovacs and UV1, you know, outside of Scandinavia, rest of Europe, US. That's where the different activities that the team members are focusing on. Okay. Good. If there are no more questions, I want to thank everybody for your, the time and your questions. Of course, a big thank you to Jens and Hans for covering the quarter report. It's a very exciting period for us and we will be hopefully sharing that enthusiasm with you in different occasions, and we will keep you up to date. Thank you.