Her er transcript fra Ultimovacs sin presentasjon @Cowen.
Har retten noen feil men prøvd og ikke endre semantikken noe så transcripten er så autentisk som mulig. Var noe dårlig lyd på slutten men tror alt kom med korrekt.
Merk at starten er noen sekunder ut i presentasjonen.
Carlos
Phase two studies, all of these studies are randomized comparative, but we also have long term phase one data showing a very good safety profile and also long duration of immune response. After seven years, eight years post vaccination, we still find T cells circulating that are educated to recognize cells expressing telomerase. And as you will see we are in a very exciting period for the company as we out of these. Five phase two studies that we are running, two of them are going to read now during the first half of 2023. We submitted the phase one data to the FDA and we received fast track designation for combination with both ipilimumab and pembrolizumab and also offer orphan drug designation. We also received a lot of interest from specialized oncology groups and the pharma companies. So we have a lot of collaborations in this very broad development program. A little bit on the financials, the company was founded in 2011. And we did an IPO in Euronext Oslo Stock Exchange in 2019. After that we did the two direct placements and so we have it now at the end of the Q4 2022 about $42 million in cash what gives us an expected runway to meet 2024. So very good place to be in these very volatile times. Our market cap is as you can imagine varies, but is approximately $400 million and. we are small company with 26 people located primarily in Oslo, Norway, but also in Uppsala, a city north of Stockholm. In Sweden. Our main shareholders are very big family offices, but also some institutions like the Norwegian Pension Fund and these are all very long term investors. About 70% of the company are in the hands of the the top 20 investors, so with a very long term perspective. But of course allows the company to focus on the business. And with this, I give the word to Jens that will talk you through the science, but also the clinical results and the clinical development program and then I will pick it up after that.
Jens
Thank you, Carlos so. So this slide is presenting the current clinical program in Ultimovacs and that pre top line represents our lead indication malignant Melanoma. We have conducted 2 phase one trial where we have results and we also have a third trial which is a randomized phase two trial fully enrolled which we expect readout from the first half of this year. Over the last years, it has been a lot of attention from other academic groups and also other pharma companies. So we participate in four other randomized phase two trials, one in mesothelioma patients, one in head and neck, one in ovarian cancer and one in non small cell lung cancer. Out of these four trials the mesothelioma trial is also expected to have a readout of the results first half of this year. Moving on to our hypothesis around how the vaccine is working. So as you know over the last decade checkpoint inhibitors have shown that if they unleash checkpoints and between the immune system and the cancer cells in some patients, you can see very good responses. This is due to the pre-existing T cell in T cells in that patient that can kill off the cancer, but in most patients. you do not see a sufficient efficacy from the pre-existing activating T cells in the patients. So other strategies is also needed to help these patients come into a complete response. We are developing a cancer vaccine that targets some antigen called telomerase. So a short background, so normal tissue to become tumor tissue different hallmarks need to be in place. For example, the cancer cells need to have a strategy for eternal cell division and then 85 to 90% of cancers the tumor cells have turned on and enzyme called telomerase to be in search of position. This is something that happend early in the development of the tumor and it’s also something that followed the tumors throughout the course of the cancer. So you can find this from early stages and in the primary and in the metastasis of the tumor. We have tried to illustrate the telomerase as an antigen in this street to the right, so we call this a truncal event. And the red color represent the expression of telomerase, and you can see over time that the telema race is also going out in their branches of the tree. This might be in contrast to some new antigens, which you can find in branches of the tree, but will not represent the full tumor, because it’s very important to emphasize that telomerase is an essential for that tumor cells. They cannot stop expressing it. If they do so, they will not be able to divide forever anymore. The vaccine itself consists of three long peptides. We are focusing on CD4 expansion with this vaccine. The three peptides cover a sequence from the catalytic site of telomerase and they are by intention placed there. So it will be difficult for the tumor to mutate itself away from recognition from the immune system. Also further in the three peptides there are several epitopes that can be bound to different HLA molecules high frequency agile molecules? So we do not do any HLA screening of patients prior to inclusion in studies. In our first phase one trials, we saw that between 80 and 90% of patients and have an immune response with this strategy, the vaccine itself and we vaccinate in intradermally on the belly, it’s 8 vaccinations in total, 4 vaccinations the 1st 10 days and thereafter we combine. And vaccinated with the same frequency as the drug. So they are combining with and we are always combining with checkpoint inhibitors. They believe there is this mutual interaction between checkpoint inhibitors on one side and the immune system on the other side. And after the expanded T cells are part of the immune system. We do combine with what is standard care in different indications or close to be so. Some words about the phase one trials in our lead indication malignant Melanoma. So we have conducted 2 phase one trials, one where we combined you have one with equilibrium in stage four patients malignant Melanoma and one where we combined with pembrolizumab in the in advanced malignant Melanoma or metastatic malignant Melanoma. For both these trials we did see a good safety profile and by that then we are meaning that what we see is the safety profile of the checkpoint inhibitors we are combining with except for injection site reactions. Also for the first trial with which I had 12 patients, we did see in response rates in one. Third of the patients, one complete response and three partial responders. Over the next few slides I will go to the efficacy signals from the UV1 Pembro trial. Most of these trials have been presented and published different places. And for the UV1 Pembro trial, it was presented at that school 2021 and also it was part of the plenary session at the SMR Conference in Edinburgh prior to Christmas. We have sent off the data from these two trials to the FDA. And received back fast track designation for both combinations and also orphan drug status for the vaccine in malignant Melanoma. For the 30 patients, I mean the UV Pembroke trial, you can hear see the development of their cancer. This is the spider plot of the 30 patients. Each line represents the patient and each box represent an image. 57% of the patients had a partial or complete response in this trial and we have also followed this patient for two years and we see after one year that 94% of the patients remain in response at that point. Here in this waterfall plot, you can see each column represents the patient and you can see the stage of the disease at the top of the columns or below. And also we have some information about different biomarkers. I will come back to that. But first of all as I said, we saw complete response in 1/3 of the patients, 10 out of 30 patients and a partial response in seven of 30 patients for your information beyond and below the waterfall you can see the numbers from the keynote 06 trial, which was the registration study for pembrolizumab alone. As you might know in this large studies for the CPI for example the keynote 006 trial in retrospect it was analysis done of different biomarkers like PDL one expression, tumor mutation burden and others. And they also found that if you had a PDL one negative trial patient, it is less likely to respond to the checkpoint inhibitors as compared if you have high PDL one expression. We also did this. Analysis in our study. As you can see in the table to the right and we actually saw the same response rate in those patients and with the PDL1 negative status as in the whole study as such, both when it comes to response rate, but also for the complete responders. And this was also true for the other biomarkers we analyzed tumor, mutation burden, interferon, gamma signal or signature and T cell infiltration. On this slide you can see a overview of the five phase two trials we are participating in. So they want to the left, they need some trial is our sponsor trial. The four other trials are studies where we participate except for the study in middle the focus trial, all of these trials are endpoint driven. So there’s the predefined number of endpoints we are waiting for in this trial to occur and when that happens the database is closed and we will thereafter follow the patients for overall survival over the years after. In the Initium trial Ipi+Nivo is the CPI and the plus minus the vaccine on top. As I said, this trial is fully enrolled and we expect readout first half of this year and primary endpoint is hazard ratio PFS. For the mesothelioma trial , it’s also Ipi+Nivo which is the CPI plus minus the vaccine. Also this trial fully enrolled and expect readout first half of this year the focus trial in middle and head and neck cancer. This is the Pembro indication. So it’s pembrolizumab plus minus the vaccine on top. If this is a landmark trial, so half a year after last patient has been included, there will be a readout of the primary endpoint which is also here PFS. The last two trials the DUVAC trial in women with the Ovarian cancer, BRCA negative ovarian cancer, the patients that are receiving either Pula Padim, Olaparib durvalumab or Olaparib durvalumab and the vaccine. In the last trial long back trial, we have the patients have PDL1 50% or above without the mutations and this is similar to the pembrolizumab indication or label. So in this trial we use Semi Plymouth and then price minus vaccine on top these two last trials that nubuck and landmark trial has quite recently started recruitment. So as you can see from the numbers at the bottom. Just a little bit more discussion about the these two trials. So the initial trial is our sponsored trial, it’s a trial that was including patients in the US and Europe fully enrolled as of June last year and we expect readout this year. First half of this year. PFS is the primary endpoint and the statistics is with the hazard ratio 0.6 and alpha 0.1, power of 80.
Jens
For the NIPU trial, the statistics is quite similar to the Initum trial, also here and we combined with Ipi+Nivo CPI plus minus the vaccine on top. We find it quite interesting that after we started this trial Ipi+Nivo became standard of care for this patient group both here in the US and also in Europe. So to finalize this clinical part of the presentation, I would say that that from the phase one trials I think we have had seen a very good safety profile that has not stopped us in developing the vaccine in different phase two trials. And also on the efficacy side where we think we have seen a good response rrates in different patient populations for example, both those with the low PDL1 and as compared to the whole group as such.
Carlos
Thank you Jens. So let’s talk a little bit about the, the potential for the use of UV-1 this looks like a, you know a busy slide but it’s it’s a good slide to show you. You know we, you see on the on the left a list of different cancer types and then you see the green boxes in the different indications where the checkpoint inhibitors are already approved as standard of care in the darker blue is types of tumors where we UV-1. Of being or was used. But here I want to emphasize the fact that you know when you look at the 10 or more indications in light blue, these are other indications where we could be running clinical trials. We already have five studies running, but you know with unlimited financial resources we could be running an additional 10 indications. And this of course this is just to show you that as long as the cancer is expressed telomerase what is a lot of them and there is a checkpoint inhabitor approved or in the final stages for approval. We can be used in those indications. So a lot of potential for growth of UV1 in additional indications. Also as you know very recently the checkpoint inhibitors are migrating more into the neoadjuvant and the adjuvant a part of the the treatment. So new adjuvant is an area also that as a vaccine would make absolute sense for UV1 to be part of the thermal mentor. So we we are looking into the this as another potential for growth. So all of this is really emphasize the the, the value for UV1 in a very broad usage and if you see that we are being combined with five out of the top 6 selling checkpoint inhibitors and you know then then really the size of the market for the checkpoint inhibitors you see that you know there’s a lot of potential for. UV1, so not only in terms of the indications and the broad usage but also as already Jens mentioned because we have some key competitive advantages versus other approaches in this space. So we are using to easy to use intradermal injections. We are a truly off the shelf product being kept as a dry powder in a normal fridge and then reconstituted with sterile water. We don’t need to do any pre screening of patients. We don’t need to do any biomarker analysis in order to enroll patients. So very easy to treat these patients you know and really allowing for easy access for patients even if they are not close to very specialized centers.We have a simple manufacturing process. We work with one of the leading peptide manufacturing in the world, polypeptides and very importantly you know we by the time we are ready to move to the next phase of development, we are going to have a commercial process. In place what is very important for partnering discussions but also for potential discussion with the authorities for accelerator conditional approval. If the data is very positive, it’s three we pass already 3 shelf life. So nothing really complicated when they think this is a very key advantage when the patient needs to be treated with UV1, but let’s talk about what what comes next. We as a company we are recognized by basically delivering. On what you promised to market, but we are really now at the time where it’s a very exciting for the company as Jens mentioned we have the two to trials, the Initium and the Nipu trial reading now the first half of this year. And this is due to the fact that despite these studies starting to enroll patients in the middle of the pandemic in June 2020, the team did a great job working with the investigators to enroll these studies fully during the pandemic in a very good Time. And if these studies are positive, of course you know this will trigger a series of initiatives that the company is already preparing for. One of them is discussed with the authorities in terms of what is going to be the next phase of development together with several advisory boards that we are planning. And if the data is very positive, as I mentioned to discuss with the authorities what would need to be required for us to get a accelerated or conditional approval. On the other hand, you know we as a company we’ve been in touch with the strategic partners as a company we are prepared to move to the next stage of development. We can do that at 1-2 indications. I think that is important that is secure. But we have been publicly in saying that to you know we have a strategic partnership with the big farma that allow to expand the clinical program and of course give access to a bigger number of patients who have access to everyone in multiple indications, so these. activities will of course accelerate on the back of positive data and also you know, we continue to introduce the company to more and more investors. You know, we are of course very well known in Scandinavia in the northern part of Europe, but we have been introduced in company, you know, across Europe, the US and other regions because I think that if the data is positive will be transformational not only for the company and for cancer patients but also for the space, you know. In a series of meetings you know we receive a lot of encouragement from farma and investors because as all of these studies are randomized and comparative. If these studies are positive we will be the first company with the universal vaccine and with comparative data that showed the concept that cancer vaccines work. And a lot of people are hoping that this is the case because there is a lot of value for for patients and of course we don’t have just these two studies then the. At the next study we’ll be reading in the first half of next year and then we’ll come the the Dovacc ovarian cancer and the lung back in in lung cancer. So as a company we have multiple events coming soon. So as as takeaways as a company we are developing universal cancer vaccines to really enhance the efficacy and durability of the other immunotherapies. We can be used across the board that in multiple cancer types and in combination with multiple immunotherapy combinations we have the key advantages namely that we are off the shelf and easy to use. We have shown a very good safety profile that as you know is very important particularly when you start treating patients with combination of two drugs, three drugs. showing a very good safety profile is very important in that space when when we treating with seriously adverse patients and we also shown that you know the immune response that. Induced as a long duration the broad development program really shows the strong potential for a very big commercial potential. And the five phase two, five phase two randomized trials that are ongoing also have the possibility to to show that we have received the external validation from the FDA by receiving the fast track designation and the orphan drug designation, but also from a key oncology groups and also from Big Pharma in the mesothelioma. The Bristol-Myers Squibb supplies the investigators with ipilimumab, nivolumab and in the ovarian cancer AstraZeneca supplies to road map and Olaparib. And of course this is also a validation very rewarding. We didn’t have much time to talk about the second platform that we have that that platform that is a very innovative vaccine adjuvant platform currently in phase one and with a lot of potential. We have an experienced team, a strong shareholder base that really supports the company and we had a good and expected runway to meet 2024 that really takes us across this multiple value inflection points. So I think that as a company we are in the really in the right direction and we all hope that on the back of positive data this will be transformational for cancer patients. And with this I want to thank you for your attention.
Carlos
Are there any questions?
From the audience.
Audience
We throw out a question.
Audience
You guys have two data read out the first half of this year. Can you maybe share some expectations from the competitive perspective like what should we look in that data, you know what would constitute a successful result in those two trials and also thoughts on, you know what would you need to show in order to potentially Make those pivotal studies.
Carlos
Jens. Do you want to take over? No. No, he is miked.
Jens
Yeah, yeah so. So the design of this study is the statistics in these studies, they are typical phase two statistics. So as a base case positive trials will in a way indicate that it’s covered to go into phase three development in the different indications, as I said, we have to have a hazard ratio of 0 .6 right now and that is a number that is discussed with Doctor Sarah in the US and Europe to agree on what will be a clinical relevant result in such a trial. So when this trial reads out positive with the current statistics and that is understood by the environment that this is clinically relevant for patients. That the communist situation where you start to discuss this as a pivotal trial, I guess you need a lower number and that and this is something that is discussed with the authorities and you are also advised to move forward with some kind of accelerated approval. But I guess you need the numbers below 0.5 if I personally should throw out that number.
Audience
So you haven’t discussed it with FDA.
Jens
So, so when we discuss or in general when you discuss these kind of studies with the the authorities you are proposing something and they are going to make you aware and that the statistics and the number you have is can lead you to this and this different scenarios and to be in a position for kind of conditional approval and we need to have a number that is beyond what we have as a base case in in our trials. So this is not directly phase three trials as such or pivotal trials…
Carlos
So just to to confirm, yes the the protocol for the Initium study was discussed with the FDA and the EMA because 50% of the patients in the study are recruited in the US so that the statistics for the Phase II study were discussing the grid by the FDA and the we know that moving to a phase three we will need of course to increase the the number of patients. And also move the primary endpoint from PFS as a ratio PFS to overall survival what is typical in phase three studies, but the the positive study will be the the next step will be moving to pivotal studies.
Audience
Great.
Carlos
I think with that we’re pretty mucho ut of time. So thank you very much. Thank you.
