Ultimovacs Asa

Good afternoon, everybody, and welcome to UltimoVAX first quarter 2023 results. As usually, I have with me Jens Björheim, our chief medical officer, and Hans Vascord Eid, our chief financial officer. You have the opportunity to ask questions, send questions during the presentation, and we added to the ones that we already received. And we will try to answer as many as possible after the presentation. So we've moved to the next slide. You know, I have to show you the disclaimer. And in the next slide for just to take in consideration that some people may not be so familiar with UltimoVAX, I'll just give a quick introduction before moving specific to the quarterly results. So UltimaVax 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 to 90% of cancers throughout all the disease stages. The vaccine is easy to use, intradermal injections, 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 one phase one and five phase two trials ongoing, and we also have multiple phase one in long-term follow-up. As a matter of fact, we have a studies being followed up for now 10 years. In these studies so far, we're showing a very good safety profile, fixed 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. We, as you will see, we are in a very exciting period for the company with very near-term equivalent inflection points, as we will have readouts from three of our five randomized comparative phase two studies. We have a strong external validation, not only by receiving the fast-track designation endorphins rate 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. So if we move now 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 five randomized comparative phase two 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 US, and Australia. 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. So very, very important milestone for us. Jens will give you a little bit more detail about the enrollment, but we completed the NIPU enrollment in January 2023, and we continue to give guidance to have the results available now in the second quarter. 2023. The enrollment in initial 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 DUVAC study in ovarian cancer, in the lung vac, in lung cancer are at an earlier stage but also now picking up in terms of enrollment and we expect readouts in the second half of 2024 and also 2025. We are very pleased to receive IP protection now the new combination pattern 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. So we as part of our strategy to strengthen as much as possible the patent portfolio for UV-1 and for other products in UltimoVAX. Very important. And despite some of these movements in terms of guideline, we continue to have an expected runway to meet 2024. And this is very important because this runway takes us through the expected results in three phase two studies. So very important to be, particularly 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 raise capital. So we are very pleased that we are not only financed, but during this period, we are going to have three potential key value 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 Dovac and the Lungvac trials, these two trials are early on. Still, inclusion is 24 patients in the Dovac trial and seven patients in the Lungvac trial. For the tender 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 Ultimax. So a few considerations around this. So as you know, the lead indication and our sponsored indication is in patients with malignant melanoma. We have conducted two phase one trials that are completed and reported. And we have a phase two 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 UV bone in different clinical trials. And as you know, we are participating in four such trials in mesothelioma, head and neck ovarian cancer and non-small cell lung cancer. So why are we present in so many different trials? So I have a few comments on this. So first, for these indications, it's important to understand that these are indications where all or almost all patients are expected to express telomerase. So 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, So telomerase is an enzyme that is allowing the cells to divide, at least in theory, forever. There's a group of different aspects around 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, and 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 prerequisited. It's something that you need to have in place to move a cell from a normal cell into a cancer cell. So the telomerase expression will be there in all parts of the tumour from the early stages of cancer and also in all parts of the tumour, both in the primary tumour and in the metastasis. And the tumour cannot turn off the telomerase because then the ability to have eternal cell division will disappear. So we know that our target is present in the patients in our indications. And as you know, from all the studies with checkpoint inhibitors over the last decades, what they actually do is that they remove a part of their resistance towards the immune system so that the pre-existing 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 cancer, as you can see in the table to the right. The black triangles represent the median PFS in these four different indications. The red columns, the response rate, and the green columns, the complete response. As you can see, 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. So as I said on the previous slides, in our clinical trials we have two 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 had proven to have good signals in larger trials. And our question is actually what happens if you add uvivon 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. So 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? And 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 two, we find ourselves in a very good position because the different biology will help us to understand the tentative model actions of our vaccine in different biology and with different checkpoint inhibitors moving forward. And this will be very valuable information for us moving into phase three programs in different indications. Just to repeat some of the signals that we have seen earlier on. So 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 one and two 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 represents one patient and each of the boxes is representing an image of that patient. So you can see the number of weeks at the x-axis and percentage change in the tumour 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 two years, and what we saw was after one year, 24 of the patients that were in a partial or complete response were still in that condition after a year. On the next slide, you can see the same patients in a waterfall plot. Here, each patient is presented by a column, and the stage of the disease for each patient is annotated above or below the columns. And also there is some information on different biomarkers that are associated with good or not that good response to immune therapy, like TMB, tumor mutation burden, LDH and PD-L1 status. As you remember, in this study, we actually saw that one third of the patients had a complete response. And also, 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 have 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%. So there are signals here that both in this small trial, of course, with 38 patients, but in this small trial, we did see that patients that were PD-L1 negative responded in 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. So these signals of efficacy, how they will translate in the phase two 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 unreal these mechanisms better in one form of biology than another form of biology. Moving on to the next slide. So the first or the sponsored trial for us, the INITIUM trial in metastatic or advanced and metastatic malignant melanoma and was fully enrolled as of July 2022. Inclusion of patients were conducted in the US, UK, Belgium and Norway. And this is a so-called endpoint driven study, meaning that based on historical data and the statistics and the inclusion rate in this study, we wait for 70 endpoints to occur. As we informed in end April, those 70 endpoints had not occurred as of late April, and 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, and it means that they progress or die at a 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 with the same inclusion and exclusion criteria, where we will have a lot more information about each of the patients. There will be liquid and solid biopsies at different time points throughout the treatment of these patients. And for us, 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 uh 70 endpoints in the initial trial and the database for an for pfs will be locked but all patients will still be followed up for overall survival over the next years so even if so and that goes for all the patients included in in the study if you move on to the next slide Also some comments about the malignant pleural mesothelioma, which is the NIPA trial, which we expect to have a readout now in the second quarter of this year. As you know, mesothelioma is an aggressive cancer with high mortality, and there are few therapeutic options. Actually, when we started together with the OUS and Bristol-Myers, the NIPI 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. And this is somewhat good news for the patients. It improves the overall survival somewhat from 14 to 18 months in these patients. But of course, there is still room for improvement. There's mortality in this trial. 16% of the patients are without progression at two years. and 41% of the patients are alive after two years. Moving on to the next slide. The NIPI 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 before 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.

Thank you. Then we'll give a brief financial update. By the end of the first quarter of this year, we had a total cash holding of 406 million, roughly 39 million US dollars. That is down from 425 million one quarter back. We do maintain the guiding that the expected financial runway is until mid 2024. The extended time to read out in the initial trial is not expected to have any significant impact on the financial runway. Of course, there are some costs associated with the extension, but we see no need for changing the guidance. Some key numbers. The operating result, the EBIT, in the first quarter was negative minus 51 million NOK. And the profit before tax in the quarter was negative minus 34 million NOK. 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 costs 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 the 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. And the expected increase is driven by further progress in the phase two 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 over the next quarter, 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. And 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. So the lean business model we expect to maintain. And this means that when the defined ongoing projects are completed, Future burn rate will then be a function of what new projects we initiate. And that will largely depend on the outcome of the phase two trials. On the next slide, we have some more details. I would just like to point to a couple of points here. When it comes to personnel expenses, payroll expenses, The share option costs constituted 6 million NOC in the last quarter, and that is 8 million higher than the same period the previous year. So there is a significant increase driven by the development in the share price. To a large extent, these costs are non-cash costs. Also this quarter, we had a positive contribution from financial items with a net contribution of 16, 17 million NOK. And 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. So, while the total operating expenses were minus 51 million, the total loss was reduced to 34 million due to these financial items. On the next two slides, we have the regular operating cash flow illustration, and 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.