Ultimovacs Asa

Good afternoon, good morning, or good evening, depending on what part of the world you are listening to us. And we want to thank you for taking the time to listen to the UltimoVax second quarter 2023 results. As usual, I have with me Jens Bjornheim, that is our chief medical officer, and Hans Vasco de Eyde, that is our chief financial officer. I want to remind again everybody that you can use the system to put questions that we will try to answer as many as possible after we cover the presentation. And with us, briefly moving to the next slide. As a publicly listed company, we need to show you the disclaimer. And moving to the next slide, and just for the benefit of the ones of you that are not so familiar with UltimoVAX, just briefly tell you in summary what do we do. We are a clinical stage biotech, and we are developing a universal off-the-shelf cancer vaccine in quite a broad clinical program, as you will see. We have, as I mentioned, universal off-the-shelf cancer vaccine that targets telomerase. Telomerase is expressed in 85 to 90% of cancer types throughout all stages of the disease. And because it's essential for the cancer cell survival, it's also difficult for the tumor to escape the immune response. The vaccine is easy to use as intradermal injections. And as you will see, and we try to prove, has the potential to be used across multiple cancer types and in combination with different immune modulators. We have an excellent clinical trial execution. Currently, we have one phase one and five phase two trials ongoing and multiple phase one studies now in long-term follow-up. We have shown so far quite a strong safety profile, clear signals of efficacy, and also durability of immune response. Some patients still show immune response more than 10 years after being vaccinated. We are really approaching near-term very key value inflection points for the company with data from three randomized phase two studies expected within the period of one year with the first ones coming now in the fall of this year. We also have strong external validation by we received fast track designation, orphan drug designation in metastatic melanoma by the FDA. And also because we, as you will see, we have several projects that we collaborate with big pharma companies in our extensive clinical program. And we can see that in the next slide. So Jens will cover the details, but here I just want to highlight because it's really rewarding and the recognition of the dedication and excellent execution by the team that every quarter we continue to show that we are completing enrollment in our studies. And of course, as you see there, particularly the ones from phase two, that is the INITIUM, the NIPO, and the FOCUS study, you know, this is more important to emphasize that two of these studies started to enroll at the beginning of the COVID pandemic, and FOCUS also during the pandemic, and despite of these challenges, you know, we have been successful in completing enrollment of these patients. We will talk in more details, Jens will cover this, but I also want to emphasize here that what I mentioned that in two of these studies, in the NIPU study mesothelioma, we cooperate with Bristol-Myers Squibb, and in the ovarian cancer study, the DUVAC study, we collaborate with AstraZeneca. In addition to the program with UV1, our lead program, we also have an adjuvant technology platform, the TED platform that we have currently in phase one studying prostate cancer. And we will also give you a little bit more details during the presentation, but particularly we are planning a good information to the market towards the end of the year. So if we move now to the next slide and talking about this quarter, Again, from our perspective, another very successful quarter for UltimoVAX. I think that the major program, the clinical study where everybody is really keeping a close attention to is the INITIUM study. The INITIUM is a study where we treat patients with unresectable or metastatic malignant melanoma. And in the study, we have enrolled 156 patients. The study will stop to analyze the data when 70 patients have progressed or died. Very positive for these patients, this has not yet occurred. So we don't have yet 70 patients that progress or died. What of course is very positive for these patients. But the consequence for us is that we had to change the guidance where we were expecting top line results. from the second half of 2023 now to the first half of 2024. One of the things we are observing is a slow progression of new events or deaths. So taking this into consideration, we are internally discussing alternatives to approaches to do data readouts. We discussed this with our advisors, and of course, any activities will have to be shared and agreed by the health authorities. But we think this is important as a company to be prepared when we observe this slow progression of number of events. The second study, the NIPU study in malignant pleuromesotelioma, We had some results presented earlier where, as you know, we didn't meet the primary endpoint. It is hazard ratio pre-EFS when the images were analyzed by central review. When the images were analyzed by the radiologists at the hospitals, then we clearly met the primary endpoint of HRPFS. And also, you know, this difference between the two arms was statistically significant. But again, Jens will cover this in more detail. Very important for us was also we saw some improvement and some difference in the overall survival between the two arms in favor of the UV1 arm. Of course, this data was still not mature enough. These patients have continued to be followed. And the lead investigator and her team and the other investigators are now updating all this data. And full details will be presented, including overall survival, at the medical conference before the end of the year. So very exciting period. We are all really looking forward to receive the details of what we believe are quite exciting preliminary results. Very pleased also to have concluded enrollment in our third phase two study, the focus study in head and neck cancer. In this study, different from the other ones that are event-driven studies, we, the investigators, we look, it's a landmark study, what is called landmark study, and the data will be analyzed 12 months after the last patient was enrolled. And so the investigator then will communicate to us, particularly PFS and overall survival, after a minimum of 12 months follow-up. So this is expected in the second half of 2024. From the financial perspective, that will be covered in detail by Hans. You know, the main update was that now we changed guidance from a financial runway from mid-2024 to the second half of 2024. And the important thing to emphasize is that basically this runway will take us through the results of these three studies that we just touched bases, Initium, NIPU, and FOCUS. So if we move to the next slide, because a lot of other things happened during this quarter that we are also very proud of, that are not just related to the main studies. I think an important milestone for a biotech is that we have now more than 300 cancer patients that have received treatment with UV-1. And very important, as you all know, because safety is extremely important when you use combinations, UV-1 to date has no safety concerns in these more than 300 cancer patients. So a very important milestone for us to pass this to 300 cancer patients that receive treatment. The UV-103 study in melanoma in combination with pembrolizumab continues to deliver data We received very strong survival data, three-year survival data for the UV1-103 study, as all patients in the cohort two that were alive after two years remain alive after three years. So again, this is a trend that we continue to see an impact of UV1 in extending survival in these patients. We also continue to put a lot of efforts by the team and publish the data. This is very important to raise visibility of UltimoVAX and the science and the results to the medical community, scientific community, but also to the pharma community. And we publish in a very reputable journal, the Clinical Cancer Research, extensive results in clinical and biomarker analysis of the data from the 103 phase one trial. Also, extremely important for a biotech company, we continue to expand on our patent portfolio, similar to the grant that we received in the US last year. We receive now granted patents in Europe and Japan that protect UV-1 in combination with checkpoint inhibitors. until at least 2037. And then, of course, there will be post-extension. So very important that a great effort by the team to continue to strengthen our patent portfolio that, as you know, is extremely valuable on the valuation of the company in any discussions of a partnership with Big Pharma. We are also very pleased that our chief scientific officer, Gustav Godernak, that, as you know, is also one of the inventors of UV-1, was awarded with the Norwegian Tech Awards Honorary Prize as an outstanding pioneer in the fight against cancer. We are not surprised. It's a very well-deserved award to Gustav. And again, we as a team hope that this will be the first of many other awards that Gustav we'll receive as we progress and we start to get the data. As I mentioned briefly, Ultima Fox is not just UV1. We have our TED technology, adjuvant technology. In addition to the Tendu study, that is the part that is more visible to our listeners, we also have been doing extensive work in preclinical and CMC studies. And we plan to give a little bit of an update to the market on the overall TED platform technology, including the Tendu study that is one part of the overall program. And we plan to do this towards the end of the year. So with this, moving to the next slide, I give the word now to Jens. Jens?

Thank you, Carlos. Good morning and good afternoon. The first slide in my part of the presentation gives you an overview of our clinical trials in phase two. For your benefit, just a few comments around these studies. As you can see here, we are in five different indications. This is different cancer forms with different biology, and also cancer forms that are treated with different drugs. In all these indications, telomerase is expressed and we combine with what is the standard of care as of now. So for the NITIM and NIPA trial, we combine with ipinivo, as you know, in the head and neck cancer focus with pembrolizumab, in ovarian cancer with durvalumab and olaparib, and in lung vac with semiplimab. For these studies, three of them, as Carlos mentioned, they are fully enrolled. The initium study was fully enrolled last June, and I have expected top line readout now, first half of next year. For the NIPA trial, we had some of the data presented in June this year, and the rest of the data is expected in fourth quarter this year. And for the FOCUS trial, which is a landmark trial, All patients were included in August. So the inclusion took two years from August 21 to August 23. And we will wait 12 months to have 12 months information on all endpoints. And there will be a readout of this study second half of next year. The studies has been and will be also to recruit the rest of the patients conducted at sites in the US, in Europe and in Australia. On the next slide, you can see an overview of the current inclusion in the different trials. So for the three first, they are completed with enrollment. the DOVAC trial in ovarian cancer patients. It's now 37 patients, up from 24 in the previous quarter report. In the LUNGVAC trial, 11 out of 138 patients are now enrolled. These two trials are still in early days, so we expect the inclusion of patients to increase over the next period. The TENDER study with the TET platform was fully enrolled earlier this year, and we expect a readout of that one for the quarter this year. On the next three slides, we have some comments to the fully enrolled trials. The INITIUM trial is a trial in unresectable or metastatic melanoma. This is our sponsored trial. We enrolled 156 patients from 39 sites and 40 hospitals in the US, UK, Belgium and Norway. The first patient was enrolled in June 2020 and two years later in June 2022, all of the patients have been included in the trial. As of now, all patients in this trial has been followed for longer than 12 months. And we mentioned this due to the fact that the historical studies that we are used to design this study, and which is also in a way the benchmark for ipinivo, and checkmate 067 and checkmate 511 trials. Both of them have a medium PFS that is between 9.5 and 11.5 months. So as of today, all patients in this study has been observed for at least 13 months. In this trial, there is an endpoint-driven design. This means that it's defined prior to start of the study, how many patients that should have an event, meaning progression of the disease or death. In this study, it should be 70 cases before the database is closed and the calculations are done. In April this year, we informed the market that we hadn't reached 70 events in this study, and we also today informed the market that 70 events have not been reached in this study. Therefore, we extend the readout to the first half of 2024. As you know, in checkpoint inhibitor treatment, there is a plateau and most of the patients have now reached this linear plateau in the Kaplan-Meier curves for PFS. So we expect slow progression of new events over the next period of time. We will have already started internally to explore alternative approaches for data readout. And we will, of course, in due time, discuss with regulatory authorities how to proceed with the closing of the database and readout of this trial. On the next slide for the INITIUM trial, This is an investigator-initiated trial led by Oslo University Hospital. The trial is supported by us with the vaccine UV-1 and from Bristol Myers Squibb with IPI and NEVO. The study enrolled 118 patients from six sites in the Scandinavian countries, in Spain and in Australia. First patient were enrolled in June, 2020, and the last one was enrolled in January, 2023. In June, we had some information from this trial. The primary endpoint in this trial was defined as central review of images and death. According to central review, the study was negative. As a test of the primary endpoint, also other ways to assess the images are done, and one of them are local assessment of the images. This is something that is predefined in the protocol prior to the start of the study. By using local assessment to review the pictures and images, the study was positive. And by positive, we mean that according to the statistics in the study, which has been disclosed earlier, with a hazard ratio of 0.6, one-sided alpha of 0.1 and a power of 80, this study was statistically positive. Also in the June results, we saw an interesting trend in overall survival with a clinical relevant difference between the arms in the Kaplan-Meier plot, but still the data in mature to conclude. So over the months now, we are waiting for the overall survival data to mature. It is expected that the top-line data, including updated overall survival data, will be presented at a medical conference in the fourth quarter this year. On the next slide, regarding the FOCUS trial. This is an investigator-initiated trial sponsored by Halle University Hospital. This is a hospital just outside of Berlin in Germany. And this is a German trial, 10 sites and 75 patients have been enrolled in this study. Enrollment took two years from August 21 to August 23. Different from the other four phase two trials, the focus trial is a landmark study. So the primary endpoint in this study will be PFS as at six months. To relate the PFS and the other endpoints in this study, all patients will be followed for 12 months. And after 12 months, there will be a readout of all endpoints, both the primary PFS at six months and also all endpoints at 12 months. These top line results are expected in second half of 2024. I guess when we move on to the next slide now, Hans will say a few words about the financials.

Yes, thank you, Jens. I will proceed with the key financials. Move to the next slide. So by the end of the second quarter, we had a total cash holding of 344 million NOK or around 32 million US dollars. And as Carlos also stated, we have now revised the expected financial runway. We have up until now guided a runway to mid 2024. And based on updated projections, we are now changing the guidance to the second half of 2024. This means that we will have funding through the three first important readouts in the Phase 2 trials, more specifically the reporting of the overall survival data in NIPU later this fall, and the top-line readouts in NISM and FOCUS. The basis for the revised and extended runway is that Some cost elements are coming later than previously anticipated. We have not made any specific cost cuts, but have been somewhat conservative when estimating the runway earlier. And generally, we have a cost-conscious approach internally, which makes us able to capture certain cost savings. Looking at the key financials, the EBIT or the operating profit for the second quarter, we continue, of course, with the operating loss at this stage. And we had a negative operating profit of minus 51 million NOK in the second quarter. For the first half, we had operating profit of minus 101 million NOK. And looking at profit before tax, for the quarter, we had a negative profit of minus 43. And for the first half this year, minus 77 million NOK. If we look at payroll expenses specifically, the underlying salary expenses are fairly stable from quarter to quarter. But there are some significant quarterly variations in total personal expenses due to the share price-driven allowances related to the share option program. This is fluctuating with the development in the share price. And in the second quarter, we had a drop in the share price. And this implied that we had a negative cost element of around 6 million NOC this quarter. So without this change, this element, the cost would have been six million higher, just to be clear on that. Looking at R&D and IPR expenses, these are significantly higher than the previous quarters, driven by clinical trial activities and manufacturing, also called CMC activities. This is, as we have guided for quite some time now, that the R&D expense level will increase from the previous levels. So going forward, we should expect the operating expense levels to continue at a fairly high level, as we have seen now for the last couple of quarters. There will continue to be quarterly variations, but this expected expense level is driven by the further progress in the phase two trials, in the CMC development, and in other R&D activities. Being mindful of time, I will not go into detail in this presentation. As always, we have included more detailed slides on the key financials, including quarterly breakdowns of cash flow and P&L. But we would like to prioritize time to Q&A. So if there should be specific questions, please do not hesitate to contact me after this presentation, if you would like further details. So with that, we will skip the next couple of slides and move to slide 18, and I will give the word back to Carlos. Thank you.