Ultimovacs Asa

Good afternoon, everybody, and welcome to Ultimovax First Quarter 2024 Business Update and Financial Results. As usual, I have with me Jens Björheim, our Chief Medical Officer, and Hans Vassgård Heid, our Chief Financial Officer. I remind everybody that if you have any questions, you can send it to us during the presentation, and we'll try to answer as many as possible at the very end. So if we can move to the next slide, you know, I need to show you the slide. But moving to the next one, I will have a brief introduction. Jens will cover, as usual, the clinical update, Hans the financial update, and then I will close the meeting with some of news flow and before we then are available for Q&A. So moving to the next slide, I think. Good afternoon, everybody, and welcome to Ultimovax First Quarter 2024 Business Update and Financial Results. As usual, I have with me Jens Björheim, our Chief Medical Officer, and Hans Vassgård Heid, our Chief Financial Officer. Have a look. with some of news flow and before we then are available for Q&A. So moving to the next slide, I think, you know, we had the recent webcast and, you know, I want to emphasize again that we remain confident in UV1's potential and are committed as a company and as a team to bringing William of AX across the next important data points that as everybody knows are the focus and the results. We have had positive phase one data with UV1. NEPO has demonstrated clinical relevant beneficial differences in the risk of death and objective response rates. We also received positive feedback from both investigators and regulatory authorities. And there's a well-known fact that, you know, in the developing of immunotherapies, they succeed in some indications, they fail in some other ones. And this is a standard development practice to basically try to evaluate multiple indications simultaneously when the mechanism of action has a broad potential. And that's what we do with our phase two program. It's a data driven approach. We have five randomized controlled trials in various indications and the near term top-line results expected from some of these phase two trials. This is the focus. In the next came a cell carcinoma. As you know, enrollment is complete and we expect to read out now in the third quarter of this year, 2024. Dovac is in second line treatment of ovarian cancer. We are enrolling and as you saw by the numbers, you know, it's progressing really nicely. And we expect to read out in the first half of 2025. Of course, the negative initial results have had important consequences for the company. As mentioned, we have implemented cash preservation initiatives that extend the anticipated financial runway to the fourth quarter 2025. This is very important because it takes us beyond the anticipated top-line results of both focus and Dovac trials. In the next slide, you see basically that also in addition, and this as I mentioned, positive feedback from the authorities that we've received in February this year, both the European authorities orphan drug designation and from the FDA the fast-track designation. And these are together with previously received at the end of last year, the orphan drug designation from the FDA. So all this data in Mesotelioma, these designations were based on the data that was presented at ASMO in the fall of last year. So if we move to the next slide, basically to reinforce my previous statement, it is really important for companies, particularly for biotechs, to have multiple clinical trials. As I mentioned, this is a standard practice in big pharma companies. They have many more trials running in parallel because it's expected some will fail, some others will succeed. And fortunately, we have more than just initial study melanoma. And that's why we continue confident and really committed to bring these results and these trials to the next phase. So with this, I give the word in the next slide, we're moving then to the clinical update. And I give the word to Jens. Jens, please go ahead.

Thank you, Carlos. Good afternoon. So in this part of the presentation, I will have a few slides on the background for our program. Data from the phase two trials that have been reporting over the last year. And also look into the future with the next upcoming phase two trials that will report. So first on the next slide, the background for our phase two program as it stands today. Going back a few years in time, we had three phase one trials and also somewhat later a fourth phase one trial. Based on the results from these phase one trials, we did see a long and good immune response to borstelmurase. So a good safety profile for the UV1 vaccine. And we also saw efficacy signals, both as a monotherapy and in combination with the checkpoint inhibitors. Based on these results, we were encouraged to move into phase two. In that phase two program, we decided to move into indications where and tell them race our target for the UV1 vaccine. It's expressed in all or almost all cancer patients. Also to move into different biologists, because at that time point, we didn't know the mode of action of a vaccine. So it's important to capture any efficacy in different biologists. Also, we wanted to combine with different checkpoint inhibitors, both as a combination with one and also a combination with two different checkpoint inhibitors. I will come back to this. And also we have a sample tissue from patients in these different indications so that we can get a better understanding of the mode of action of the vaccine and how it works together with the CPIs. Moving on to the next slide. So there are two main groups of checkpoint inhibitors. It's the PD1 and PDL1 and then CTLA-4 antibodies. For the CTLA-4 antibodies, it's expected that if you add those, you can see a stronger vaccine induced T cell response. The -CTLA-4 antibodies allow expansion of T cells a longer time and stronger than if it's not there. So you would have a stronger immune response. For the anti-PD1 or anti-PDL1 antibodies, in several indications, those antibodies are approved. In some of these indications, it's observed that the patients lack a sufficient tumor repertoire with activated T cells against the tumor. So adding a vaccine that expand T cells that is relevant in that tumor is a good hypothesis. The combination of these two allow both for higher expansion of T cells and also adding T cells in for patients that have a low or small repertoire of T cells. Moving on to the next slide, just to show where these two antibodies are working in the body. So first up to the left, the two yellow circles represent lymph nodes and an antigen presenting cell presenting an antigen to the immune system. When we are vaccinating or when antigens are leaking from the tumor at the bottom, those are presented to the immune system and T cells are expanded. In the normal body without any treatment, this expansion of T cells will be turned off after a while so that you don't end up with a huge number of T cells towards a specific antigen. By adding anti-C4 antibodies, you take away this break so that the expansion of T cells continues and it's expected that you will have a stronger immune response. So for down to number two at the bottom, the PD-1, PD-L1 antibodies, they work in the tumor and in the draining lymph nodes. When the tumor grow, it will be identified as foreign by the immune system and the tumor will also recognize this. To protect itself from the immune system by other things, it starts to express PD-L1 saying to the immune system that don't kill me. By adding an -PD-1 or -PD-L1 antibody, you are taking this mechanism away, allowing the T cells, activated T cells in the body to enter the tumor and also increase efficacy of immune responses in the draining lymph nodes from the tumor. Adding these two drugs then gives more effective T cell expansion and also hopefully more effective T cell killing in the tumor. Moving on to the next slide, you can see an overview of our phase two trials. So we have trials, as I said, in different biologies. The common denominator for all these trials is that they express telomerase. In the different indications, we have combined with the CPIs that are either approved as standard of care or have shown good clinical efficacy in randomized trials. In two of these trials, we have combined with the combination of Ipilibumab and Nivolumab in the Nipu and Inicium trials, and we have results from these two trials as of now. Coming up is three trials in head and neck cancer, ovarian cancer and non-small cell cancer, where we combine with either PD-1 or PD-L1. The first of these trials to report will be the FOCUS trial that report third quarter this year, and the next one in line is the DoBAC trial, first half of next year. A few words about the results in the first two trials that have results as of today. First, the Nipu trial on the next slide. Just a small recap. So in this study, 118 patients were randomized to Ipilivumab plus minus UB1 on top. It was including patients in Scandinavia, Spain and Australia. The results were presented at ESMO last autumn, and it's expected to have an update of overall survival this year. For the results as such on the next slide. In this trial, we did not meet the primary endpoint of PFS reviewed by Central Review. There were also predefined analysis on local review of the PFS, which showed differences between the arms. Also, we did see in the study results reduction in the risk of death with 27 percent and also a near doubling of the response rate in the UB1 arm, 31 percent versus 16 percent. Based on these results, the FDA granted us orphan drug designation and fast track designation. When it comes to safety in this trial, we did not see any extra safety signals from UB1 on top of Ipilivumab, which is of importance in this quite toxic combination. And also, this is a beneficial safety profile moving forward with the UB1 development. And the lead in investigators and regulatory authorities think that the mesothelioma indication should be further explored in new clinical trials based on the results. Also, just a few weeks back, it was a publication on this study in the European Journal of Cancer. And with all the results from this study, including subgroup analysis, and we do find the epithelioid subgroup especially interesting and moving forward in this indication. Moving on to the INITIUM trial, our sponsored trial in malignant melanoma. So these are advanced melanoma patients that cannot go through surgery. And it included patients in the US, UK, Belgium and Norway. Top line results were reported in March this year, and there will be an abstract presentation at ASCO in June. Also, there is a supplementary study, a single arm cohort where we have captured biopsies, liquid and solid tumor biopsies from the patients to further understand the mode of action of the vaccine. Moving on to the next slide. So in this trial, the safety profile of UV1 was as we saw in the NIPA trial, no extra signals on top of the IPNIVO combination, which is good. This trial was a negative trial. It was negative for the primary endpoint, the PFS, and also for the secondary endpoints. And this was a surprise for us, but we will further try to understand moving forward where to place the UV1 vaccine in different indications. For this indication, UV1 on top of IPNIVO in this study did not show any clinical benefit. The supplementary study will report at a later time point, hopefully this year. In that study, we do want to find more, try to find more evidence for how the vaccine are working within this indication. And then moving on to the next slide, trials in line. So we have now reported from two trials with the combination of IPNIVO. And moving now over to a combination with a single CPI, Pemberly's mob, Durvali mob and Semipli mob in three different indications. The first study in line here will be the FOCUS trial. On the next slide, you can see the design. It's a head and neck cancer trial. It's in patients with metastatic or recurrent head and neck cancer that express PD-L1. For those that express PD-L1, a standard of care is Pemberly's mob. And in this study, the patients are randomized to Pemberly's mob plus minus the vaccine on top. 75 patients in total. Top line results are expected in Q3 this year. The head and neck cancer group, as you can see on the next slide, is a group of cancers that arise from the linings. In the oral cavity, in the pharynx, larynx, lips, in the upper part, in the throat. It's the seventh most common cancer globally, so it's a large indication. In this indication, also telomerase is expressed in all patients. And Pemberly's mob, which we combine with in our study, is considered a standard of care for patients. We look forward to the results in Q3 this year. Moving on to the next slide, the Dovac trial in ovarian cancer. So this trial is in women with a BRCA negative ovarian cancer. If patients respond to the second line or round of chemotherapy with a partial or complete response, they can be included in this study. All patients are treated with OLA-parib. In the experimental arm, it's OLA-parib plus durvalumab, which is a PDL-1 antibody, and the vaccine UV-1. This trial is enrolling patients as of now. Per now, it's 99 patients included in this trial. And top line results are expected first half of 2025 in the Dovac trial. So this is the second most on the next slide, the second most common gynecological malignancy, and it's a leading cause of death from cancer in women. Ovarian cancer is the 18th most common cancer overall. The standard treatment for these patients are surgery upfront and then chemotherapy with maintenance treatment with part inhibitors like OLA-parib or wevvacucimab. Several studies have showed added efficacy when part inhibitors are combined with checkpoint inhibitors. And in this trial, we also combined with the vaccine UV-1 on top. Also in this cancer, telomerase is highly expressed in all patients. The last trial is the L'anvac trial. It's more in the early days still in non-small cell lung cancer on the next slide. This trial is a Norwegian trial in patients with the PD-L1 expression above 50% non-small cell lung cancer without the targetable mutations. All patients who receive semiplimab, which is the standard of care in Norway, and UV-1 on top in the experimental arm. The top line results is expected first half of 2026 in this trial. Then we move on to the financial part of the presentation. So I give the word to Hans.

Thank you, Jens. So we will give a financial update following the first quarter. And to start with the funding situation, by the end of the first quarter, Utrem Marks had a total cash holding of 220 million NOC or roughly 20 million US dollars. And following the negative initial readout, Utrem Marks has made an implemented activity level prioritization and made operational adjustments to sustain the financial runway, as Carlos mentioned. And this includes a workforce reduction of approximately 40%. The cash preservation initiatives extend the anticipated cash runway to the fourth quarter of 2025, which is then beyond the expected readout of the FOCUS trial and the DOVAC trial. Based on the current plans and forecasts, the cash burn rate towards the end of 2025 is then estimated to be at a level around 15 million NOC per quarter. Looking at the first quarter 2024, we had an operating profit EBIT of minus 29 million NOC and a profit before tax of minus 23 million NOC. The main operating expense item is R&D and IPR expenses. And this was slightly lower in the first quarter of 2024 compared to the previous quarters. Looking ahead, we expect that the operating expense levels should be expected to continue at the fairly high level for some time. And then the operational adjustments and workforce reductions will start having an effect over some quarters. So during this year, we should expect not to see too much effect, but for 2025, we should expect to see a more significant effect on costs from these actions. Moving to the next slide, we go more detailed into the P&L and starting with payroll expenses. In Q1, we had a significant one-off item, which made the total payroll expenses being significantly lower in the first quarter of 2024 compared to the same quarter one year back. We had actually a negative cost of 2.4 million NOC in Q1 2024 compared to a cost level of 21 million NOC in the first quarter of 2023. The regular salary costs were slightly higher in Q1 2024 compared to the previous year. The big difference here is the share option costs. Due to the significant drop in share price following the initial readout, we have made a reversal of the social security tax accrual related to share options. This fluctuates with the company share price and this full reversal implied a positive accounting effect of 21 million NOC this quarter. The main cost item R&D and IPR expenses were approximately at the same level in Q1 2024 compared to Q1 2023. The main drivers of R&D costs in the first quarter of this year were the initial trial and manufacturing or so-called CMC activities. For other operating expenses, there were no major changes from the previous year. Moving ahead to the next slide and looking at operating cash flow. The negative operating cash flow in the first quarter of 2024 was approximately 46 million NOC, then in minus. This is higher than the operating profit or EBIT or roughly 29 million NOC. There was an error in the material that was distributed this morning. Here it's said 23 million instead of 29, so it's corrected in this version that we now share. And the difference here between the operating cash flow and the EBIT is primarily due to this reversal of the social security tax accrual that we just described. Looking ahead, we should expect continued quarterly variations in the operating cash flow. But due to the cash preservation initiatives implemented and also completion of some of the main activities, we should over time expect them to see a decrease in the quarterly costs and operating cash flow with particular effect from 2025. We have, as always, added a more detailed slide on a quarterly basis, which may serve as a reference for those wanting to go into more details. With that, we continue to the last section and I give the word back to Carlos.

Thank you, Hans. Thank you, Jens. If we move to the next slide in terms of news. And on the next slide. Yeah, so, you know, we expect now in the second quarter an update on the survival of the 103 study where we combine with Pembrokesh Mob in melanoma. And also, Dan has mentioned in the third quarter, the top line results for the focus study that then the investigators are, you know, have the ambition to present at the medical conference and post the results. And then as also mentioned, you know, we moved into 2025 and then we expect in the first half the top line results from the DUVAC trial. And then, you know, towards 2026, the LungVac study. So, you know, we it's going to be important to the middle of this year with Q3 with the focus data as this is a totally different tumor type and a different combination with the single agent Pembrokesh Mob. So if we can move to the next slide, I want again to emphasize that we, you know, continue to believe in the potential and are truly committed to bringing UltimoVac across the next important points as several times mentioned the focus and the results. I think it's encouraging to know that investigators in the ongoing trials are also committed to bringing UV1 across the next important data points as you can see from the enrollment in the DUVAC trial. We maintain and changed our strategy for the development of UV1 that focused on the randomized control phase two program where we explore the activity of UV1 in the diverse cancer types and in different immunotherapy combinations. And of course, the strategy has proven to be a wise one because, you know, as is standard, we have to expect different outcomes in all these different trials as these deal with different biologists in different tumor types and different combinations. We continue on course with our phase two program, you know, particularly as I mentioned with the focus and the DUVAC trial. And the cash preservation initiatives have extended the anticipated cash runway to the fourth quarter of 2025. What is extremely important because this carries the company beyond the anticipated top-line results for both focus and DUVAC trials. And with this, I want to thank you for your attention. And we open the floor to Q&A. Hans?

Yes, thank you, Carlos. The first question is related to finance. If the focus trial comes in negative, you probably should cut more costs to prolong the runway to cover the readout of the Lungwai trial. They have a plan for that. And I'm happy to address that. This is not something we can comment specifically. But I can give the general comment that, of course, management together with the board continuously evaluates what's the best use of the cash and the funding situation of the company. So this is, of course, something we continuously evaluate. But we cannot give specific comments on these type of questions, unfortunately. OK, the next question to Jens, I guess. It would be very interesting to follow the overall survival numbers from INISIUM. Could these results still be revisited at a later time?

So the INISIUM study as such has reported now and we did not see any differences in different clinical endpoints, including overall survival. In a different situation where we could have followed these patients for several years, that would have been interesting. With the current situation, we will not be able to follow the overall survival of these patients over several years, not as an initiative from Ultimax as such. So I agree that would have been interesting, but it's not possible to do that with the current situation. Nevertheless, the study as such was a negative one and we need to move on to other combinations and indications. This is common in this industry. Instead of using a lot of resources on this trend now, we are eager to find new ways to see if there is a home for UB1 in other combinations and indications.

OK, one question also to you, Jens. Have you learned anything about the vaccine this far, which can be used to enhance the chances of success in what remains of ongoing trials?

So as we have stated several times, so upfront, we do not know too much. This is in contrast to, for example, TKI's that are directed towards a specific mutation. Then you have some idea what kind of patients you should include in your trials and those with that mutation. For a vaccine that have a potentially very broad indication where telmorase is expressed up to -90% of cancers, it's very important to know how to do trials in subgroups or specific indications before you have done a broad clinical program. So it is by intention that we are doing trials in different biologies and different combinations. We have learned some things now. Of course, it's only hypothesis in the melanoma trial. It seems like EpiNivu is doing the job. You don't need UB1 on top in that indication. But still, we believe that UB1 has clinical efficacy. We just need to find a place for the vaccine. The next trials are in three different indications where we combine with monotherapy and experience from other academic groups and other company. So I've shown that adding different medical modalities on top of PD-1 or PD-L1 gives extra efficacy for patients. So we have to do the trials and then look at the results. And when we do have a trial with positive results, it's easier for us to further understand where to move in the future.

Thanks, Jens. One more question to you related to the INITIUM trial. In the ASCO presentation, will you give any comments to the results of the INITIUM supplementary study? And can these results say something more to the probability of a statistically type 2 error in the INITIUM main study?

So the single arm cohort will not be presented at ASCO. So it's the INITIUM results that will be presented. So the abstract is put together and submitted by the authors of the or investigators in the INITIUM trial. And it will include all relevant endpoints and safety. And hopefully it will lead to a discussion leading forward to new combinations with UB1. For the single arm cohort, we do hope to be able to present something this year. Just want to say that since the INITIUM trial is a negative trial, it's important to understand what we can get out of the single arm cohort. We can get some information around immune responses and how the T cells we activate are behaving in the body, where they are going, etc. But since there are no difference between the Ipinevo and the Ipinevo vaccine in the INITIUM trial, we do not have two different groups that we can compare as such.

Thanks Jens. That was the last question. So not many questions today. I guess that reflects that we had a major webcast less than three weeks ago. So no big news events since then. So Carlos. OK,

so thanks again to the team. And I want to again to emphasize that unfortunately we have to see some colleagues leave the company, but all the team members that stay in the company are totally committed to, again as I mentioned, to continue moving ahead with the UB1 and all the activities to really carry the company and take us to the next data points that are primarily the focus and the default trials. So with us, I want to thank everybody for taking the time to listen to us and we stay in touch and we will bring you more updates as soon as we get and particularly related to data to be presented at some medical conferences. With us, I want to thank everybody and wish you a good rest of the day.