The other big activity that positive readouts would intensify is discussions with potential partners. The feedback we have received so far indicates that they all recognise that our studies are well designed, and they realise that not many biotechs perform these types of comparative and randomised studies. So, clearly, if we have positive readouts, this will mark a path for us to engage in deeper discussions with potential strategic partners for out-licensing of UV1 and maximising the product in multiple indications into eventual phase III studies.
4 Likes
Med ref til denne posten:
Med den rekrutteringen som ble rapportert nå på Q3-pres, så ble min anslåtte LPD flyttet rett over en måned fremover i tid, og havner akkurat på julaften. Det påvirker utregningen jeg gjorde i denne posten litt, men ikke mye. Eventfordelingen som impliserer at primærendepunktet på HR=0.6 blir møtt skjer ni dager før.
Her er oppdaterte datoer:
| Dato | PD events control | PD events UV1 | Chi-square test | |
|---|---|---|---|---|
| 12 Sep 2022 | 28 | 41 | ||
| 28 Sep 2022 | 29 | 40 | ||
| 14 Oct 2022 | 30 | 39 | mPFS control | |
| 30 Oct 2022 | 31 | 38 | ||
| 13 Nov 2022 | 32 | 37 | ||
| 28 Nov 2022 | 33 | 36 | ||
| 12 Dec 2022 | 34 | 35 | ||
| 26 Dec 2022 | 35 | 34 | 0.8518 | |
| 10 Jan 2023 | 36 | 33 | 0.5752 | |
| 23 Jan 2023 | 37 | 32 | 0.3503 | |
| 8 Feb 2023 | 38 | 31 | 0.1910 | |
| 26 Feb 2023 | 39 | 30 | 0.0927 | |
| 16 Mar 2023 | 40 | 29 | Primary endpoint | 0.0399 |
| 6 Apr 2023 | 41 | 28 | 0.0152 | |
| 28 Apr 2023 | 42 | 27 | 0.0051 | |
| 21 May 2023 | 43 | 26 | 0.0015 | |
| 18 Jun 2023 | 44 | 25 | 0.0004 | |
| 19 Jul 2023 | 45 | 24 | 0.0001 |
21 Likes
Det er nok en konseptuell forskjell i det jeg gjør i mine to utregninger, kontra det @Boblegutten gjør i sin foreløpig ene i simulering av INITIUM, som jeg mistenker at mange ikke har skjønt helt.
Det jeg gjør er å si når det er mest sannsynlig at vi har x-antall events i kontrollarmen, dermed si hvor mange eventer det maksimum er i den eksperimentelle armen, og dermed hvilken kliniske effekt UV1 minimum har på et gitt tidspunkt. Altså MEST SANNSYNLIG.
Det @Boblegutten har gjort er å ta utgangspunkt i at UV1 har en klinisk effekt lik primærendepunktet, og så simulert hvilke datoer 70 events (i INITIUM altså) kommer på i sorterte/filtrerte utvalg. Hans metode starter på en måte med svaret, nemlig hvilken kliniske effekt UV1 har, men det veldig verdifulle den gjør er å si noe om spredningen rundt de mest sannsynlige datoene, og hvor sensitiv avlesningsdatoen er for en evt. friskere eller sykere pasientpopulasjon. Det boble sine simuleringer også gjør kontra mine, er å gi en nøyaktig HR, mens mine utregninger bare gir eventfordelingen som impliserer den HR som er primærendepunktet (men som altså Ultimovacs sine statistikere har regnet ut at mest sannsynlig skal stemme da de designet studiene).
42 Likes
Man må bøye seg dypt og takke for ekspertisen som forklarer / forteller fakta og matte
8 Likes
Minner om Boblegutten sitt fantastiske innlegg ovenfor av 13 oktober.
I simuleringen hadde han et Kaplan Meier plot datert 23. november.
Tar det frem siden det er 23 november i dag. Forutsetningene kan dere lese i hovedinnlegget hans.
INITIUM
Nytt plot:
Legg merke til likheten, men også forskjellen mellom disse to siste plottene. Samme event fordeling, 42/28, men forskjell i både p-verdi, hazard ratio og avlesning, sammenlignet med det forrige. Dette viser godt poenget at tidpunktet eventene inntreffer i forhold til hverandre også er av betydning.
1 Like
Som et tillegg til vurderingene som er gjort over har jeg gjort beregninger som viser sannsynligheten for at et visst antall events er oppnådd ved forskjellige datoer.
Beregningene er basert på selskapets innrulleringstakt vist under. Her har jeg i tillegg plottet inn covid belastningen i Norge som nye covidinnleggelser. Figuren viser at innrulleringen gikk jevnt gjennom hele Covid perioden.
Neste plot viser K-M plot fra CheckMate-511. Her ble Nivo+Ipi testet i to ulike forhold og begge armene ga mPFS på ca 10.0 måneder. Min digitalisering av dataene gir mPFS på 9.8 måneder, som er nøyaktig nok for formålet dataene er brukt til her.
Basert på disse dataene er det utført 10.000 simuleringer av INITIUM. For hver simulering er det innrullert 156 syntetiske individer og fordelingen til armene er gjort ved blokkrandomisering.
For hvert individ i kontrollarmen er antall dager til PFS bestemt ved å tilfeldig velge et tall på vertikalaksen på figuren over, og så lese av antall dager på horisontalaksen. Dvs at både dato for innrullering og antall dager til PFS er tilfeldige variable styrt av innrulleringstakten og K-M plottet.
Når dette er etablert for alle simuleringer beregnes histogrammer over fordelingen av når antall events i kontrollarmen er oppnådd. Figuren under viser resultatene fra 20 events, 35 events (dvs at kontroll og eksperimentarmen har lik effekt, som betyr at UV1 ikke har effekt) og 41 events, dvs at endepunktet er oppnådd. (FPE=First Patient Enrolled)
Basert på histogrammene etableres så sannsynligheten for at minst 35 og 41 events er oppnådd ved forskjellige tidspunkter. Dette er plottet i figuren under. Figuren angir dato langs horisontalaksen og sannsynlighet for at antall events er oppnådd. Den vertikale linjen viser datoen i dag. Som en ser er sannsynlighet for at minimum 35 events er oppnådd i dag ca 95%, mens sannsynligheten for at endepunktet er nådd (eller bedre) er ca 66%.
Tallene i parentes angir datoen det hvor en går fra undervekt til sannsynlighetsovervekt for at antall events er oppnådd.
NB : husk datarisiko.
63 Likes
Skrev jo at hvis @ketilaaj sendte meg data fra KM-plottet han hadde, så kunne jeg regne ut nye datoer basert på det. Men @ketilaaj kan jo regne selv han! Det han gjør kombinerer jo på en måte det @Boblegutten og jeg har gjort, og er jo egentlig ALT vi trenger!
Men jeg puttet nå en gang inn det KM-plottet inn i min modell også da, og da fikk jeg en mest sannsynlig dato for oppnådd 41/29 (altså eventfordelingen som tilsvarer primærendepunktet) på 26.11.22. Altså i morgen!
28 Likes
Er ikke primærendepunkt bare norsk for “Primary Outcome Measures”?
Primærendepunktet er PFS. Men primærendepunktet er også et nivå for PFS, og det nivået er HR=0.6 i forskjell mellom kontroll og eksperimentell arm. Eventfordelingen 41/29 er det som mest sannsynlig gir en HR=0.6.
Jeg får legge til at hovedhensikten med mitt innlegg og modell var å vise hvilke p-verdier og hazard ratioer ulike eventfordelinger kunne gi, og spredningen av disse. Avlesningdato ble på en måte et resultat av dette, og både min og @Polygon sin modell mangler nettopp en sannsynlighetsfordeling for avlesningsdato. Dette var derfor noe som manglet. Det @ketilaaj presenterer her er rett og slett et glimrende stykke statistisk arbeid
28 Likes
Kan man si, er pasientene i INITIUM et snitt av mpfs i de to beregningene som er utført for mpfs 9.8 og 11.5 måneder, så vil primary endpoint havne ca på nyttårsaften?
2 Likes
Transcript : Ultimovacs ASA, Q3 2022 Earnings Call, Nov 10, 2022
Presenter Speech
Carlos de Sousa (Executives)
Good afternoon, everybody, and welcome to Ultimovacs’ Third Quarter 2020 Results. My name is Carlos de Sousa, I’m the CEO of the company. And as usually, I have with me Jens Bjorheim, our Chief Medical Officer; and Hans Vassgard Eid, our Chief Financial Officer. I want to thank all of the shareholders that have been sending us question. But as we go through the slides, if you have additional questions, we want to handle during the Q&A session. Please don’t hesitate to use the system and send us your questions, and we will try to answer as many as possible after we go through the presentation.
With this, let’s move to the next slide that I have to show you is the disclaimer. But if we go to the next slide, I think we have to recognize that Ultimovacs continues on a consistent path of very successful quarterly results and achievements. We are really at an exciting period for the company as we are moving very strongly towards key milestones. And these key value inflection points to the company are the readouts for the first 2, UV1 Phase II clinical trials INITIUM in melanoma and NIPU in mesothelioma that, as you know, are expected around the corner during the first half of 2023.
We have been continuing to have a very overall a good patient enrollment. We have initiated enrollment in LUNGVAC, and now we have 3 patients enrolled. And of course, as you know, we concluded the enrollment in INITIUM in June. And Jens, of course, will cover more details about this enrollment. Also during this quarter very encouraging data, not only in terms of the 3-year overall survival that we reached the 71% in Cohort 1. So means that after 3 years in this cohort, 71% of the patients are still alive, but also very exciting data regarding biomarker in the Phase I study, UV1-103 that was presented at recent congress in hard-to-treat patients that really appear to benefit from the addition of UV1 to when they are treated with pembrolizumab or KEYTRUDA. And Jens will also cover this. We continue, we know with a very strong cash position in these very volatile times. This is a very good place to be. Our runway – expected runway takes us through the first half of 2024. And Hans will cover all these details on the financial part later in the presentation.
So I will give the word now to Jens, and then I will come back at the end. Jens?
Presenter Speech
Jens Bjørheim (Executives)
Thank you, Carlos. Good morning and good afternoon to the listeners. So we are moving to the next slide. You can see the pipeline in Ultimovacs, I know we have seen these slides several times before, but just some reflections. So the upper 3 lines in this slide represent our lead indication in malignant melanoma. We have conducted 2 Phase I trials that we have reported results from, and I will come back to that shortly. But also the third line with the INITIUM trial, which is our Phase II trial, randomized trial that we expect to readout first half of 2023. As we have discussed earlier, there has also been a lot of interest around the vaccine from other academic groups and pharma. We are participating in 4 different Phase II trials in mesothelioma, the kind of cancer you can attract after exposure to asbestos, ovarian cancer, head and neck cancer and the last one with non-small cell lung cancer.
On the next slide, you can see the enrollment in the different trials as of now. So as you know, the INITIUM trial was fully recruited June this year. We started recruitment in June 2020. So 2 years of inclusion during the pandemic. And we are very happy that this trial is fully enrolled, and we really look forward to the readout of this trial. Also in the NIPU trial, there is good enrollment, 108 out of 118 patients are enrolled as of now compared to 92 patients at last report.
In the FOCUS trial in head and neck cancer enrollment is also progressing well with 41 patients enrolled versus 27 at the latest report. For the DOVACC trial, we have earlier discussed that it has been more work than usual to start up new sites; new sites are now opening in different countries in Europe. We do not see that too much on the enrollment as of now, but we expect this to pick up over the next period of time. And then LUNGVAC trial, the last Phase II trial enrolled the first patients now over the last weeks, so 3 out of 138 patients enrolled in LUNGVAC as of now. For our TENDU trial, which is the Phase I trial with a different platform, the TET platform, we have enrolled 10 out of 12 patients to date.
Moving on to the next slide. You can here see the 2 trials that we’ll likely report first half of next year. So for both these 2 trials, they are randomized Phase II trials, meaning that there is a control group of patients, and there is an experimental arm where we have put the vaccine on top. In both these Phase II trials, they have a so-called endpoint-driven design, that means that we are awaiting a predefined number of endpoints to occur before we close the database and look at the results. And as I said, this will happen most likely first half of next year 2023. The primary endpoint in these 2 trials are progression-free survival, meaning that the tumor is growing or if the patient die.
On the next slide, you can see the results from the second of our 2 Phase II – Phase I trials in our lead indication in malignant melanoma. As you know, we have reported on most of these results already at ASCO 2021, where we saw a complete response in 10 patients and a partial response in 7, stable disease in 2 patients and progressive disease in 11 of the patients. Also, the median progression-free survival has readout in this trial at 18.9 months. New information were given back in August this year, where we reported on the overall survival for the first cohort of patients in this study, 3 years overall survival at 71%.
To the right in this slide, we have compared the results with the KEYNOTE-006 trial. There are some difference between the KEYNOTE trial and our trial. In the KEYNOTE trial, all patients are Stage 4, a little bit above 60% are Stage IV in our trial. Most of the patients that are not will be Stage III C patients. With pembrolizumab alone, it has been seen a complete response rate between 5% and 12%, we added UV1 on top in our study, we saw 33% complete response rate. And for the objective response rate between 33% and 37% for pembrolizumab alone versus 57% in our trial. I would also like to emphasize that in this study, as in the other Phase I trial for malignant melanoma, it has been a very good safety profile. Most safety that has been reported is as expected for the CPI, the checkpoint inhibitor alone, except for injection site reactions. This is very good news for further development of the drug as it doesn’t seem to add very much safety on top of the safety you expect from the checkpoint inhibitors.
On the next slide, you can see a picture from a conference that was conducted in Edinburg, a few weeks back, the SMR Conference, Society for Melanoma Research. This conference is a specialist conference for doctors and academic people working within the field of malignant melanoma. And we were very happy that we were allowed to present our Phase I data in the preliminary session there and the presentation were done by Yousef Zacharia. So that was very good for us, and I do hope that it was a good performance also for the audience. We have received a lot of good feedback on that.
On the next slide, some of the results from the earlier slide is repeated. So this is the progression-free survival to the left, reading out at 18.9 months and the overall survival curve in the middle. One thing that is important with this couple of curves is that you would like to understand how the endpoints develop over time. And as you know, for checkpoint inhibitors, after a certain period of time, the curve is flattening out, reaching in this so-called plateau where patients are in a stable condition for a long time. That is one of the things that they characterize checkpoint inhibitors and treatment towards the immune system, that there is a higher frequency of patients with long-time survival and response as compared to earlier treatment regimes like chemotherapy and small molecules.
If you go to the next slide, we can see some information on these patients in a more granulated version. To the left is so-called waterfall plot. In this plot, you can see the change in tumor size from baseline, meaning prior to treatment until the best achieved response for the individual patient. Each column represent 1 patient and you can also see 2 steep lines here, 1 at 20%. If the tumor grows more than 20%, that means that the patient has a progression that the tumor is growing. If you are below the minus 30 line or stippled line, that means that you have a response.
If it’s not 100%, it’s a partial response, but if it goes all the way down to 100%, it’s called a complete response. And this is the best response for each of the 30 patients in our study. Up to the right, you can see a spider plot. You also hear you start at 0. That will be the volume of your tumor prior to treatment. And then you can follow the volume of the tumors in your body – in the patient’s body over time. So each point here represent a new picture of each patient and every line represents 1 patient. So you can see all those patients that are below minus 30% are those patients that are in the partial or complete response.
In malignant melanoma, it’s allowed to treat all patients with different checkpoint inhibitors. So we do not do any biomarker analysis prior to inclusion or treatment of patients. Nevertheless, in the large studies that has been conducted, and the scientists have tried to understand if there are groups of patients that respond better to checkpoint inhibitors than others. And it has been seen that if you are – have a high levels of PD-L1 expression, one of these biomarkers, you can expect in a group of patients to have better response than in those patients with a lower PD-L1. When we added the vaccine on top of pembrolizumab in our study, we did not see this difference. Actually, in those patients with a low PDL1 expression, we saw an even higher response rate compared to those patients with a high PDL1 expression. This is also something we did with other biomarkers like tumor mutation burden, interferon gamma signature, et cetera, and we saw the same pattern with all the biomarkers used by the scientists to have some kind of view on checkpoint treatment alone.
On the next slide, you will see a comparison between overall survival with pembrolizumab alone and pembro plus UV1 in our trial. Also here, we have used the KEYNOTE of 6 data at 1 year and 2 years. And the overall survival with pembro was between 72% and 75% and 58%, respectively. In our trial, 87% after 1 year and 73% after 2 years. We will follow these patients over the next years to see how this curve, this capital line curve develop over time. And also for the median progression-free survival, as reported earlier, pembrolizumab has readout between 5.5 months and 11.6 months. Adding UV1 on top, we saw a readout at 18.9 months.
Moving on to the next slide. We have a short presentation of the TET-platform. So the TET-platform is our new adjuvant strategy and adjuvant strategy where we can combine the adjuvant with the peptides with different peptides in one molecule. So what we do here is that for patients or people that are vaccinated against tetanus, those patients will develop antibodies that recognize a sequence in the tetanus toxin. So they will have antibodies that can bind to this sequence. We have made a molecule consisting of these sequences and attached to that molecule, you combine different peptides. So the thinking here is that when you inject this in patients, there will already be antibodies present in the body that will bind to the molecule and the molecule will be actively taken up into antigen presenting cells, those cells that present foreign material to the immune system. To this tetanus toxin molecule, we can add different molecules, different peptides in different setups. So this gives us a huge opportunity to develop different cancer vaccines in the future.
Right now, we are in a Phase I with this project. We have a small trial called the TENDU study. In that study, we included patients with prostate cancer and attached to the tetanus part, we have prostate cancer antigens. The ambition with that study is to understand the immune responses that develops when we vaccinate also the safety profile with the drug and to understand more around the dosing, how much of this drug we should give to the patients in the future. So this will give us a lot of valuable information moving forward with this interesting platform technology.
On the next slide. We will move into the financial part of the presentation. So I give the word to Hans. Thank you.
Presenter Speech
Hans Eid (Executives)
Thank you, Jens. Moving on to the key financials for this quarter and year-to-date. The most interesting parameter here is the total operating expenses. And if we look at total operating expenses for the last quarter, we see and compared to the last year, we see that there is a slight increase. If we look at the year-to-date number of NOK 111 million, it’s a slight decrease or more or less the same as the previous year. Behind these numbers, there is a general increase in R&D expenses. But when we look at the personnel expenses, I’ll come back to the details in a second, we see that there is a reversal of some accruals that brings the total costs down. We’ll go through the details here.
Starting with payroll expenses. The total payroll expense in the last quarter and year-to-date were lower than the previous year. We – this has sort of 2 explanations. Looking at the regular salary costs, we had a slight increase in both the last quarter and year-to-date compared to the previous year as we had 2 more FTEs this year. However, the fact that we have a decrease in total payroll expenses is mainly due to share option costs. The last quarter and this year, we have the reversal of some previous expenses because these share option costs fluctuates with the company’s share price. And with the decrease in the share price earlier this year, this implied a reduction in the costs. So that’s the explanation.
Moving on to the R&D expenses. The R&D expenses both in the third quarter and year-to-date were higher compared to the same period in 2021. And this is primarily due to milestone payments in clinical trials as well as higher manufacturing or CMC costs this quarter.
Looking at other operating expenses, we have an increase from the previous year. This is primarily driven by higher activity level in areas like business development and travel expenses. Travel expenses is naturally picking up after the pandemic.
Looking at the financial items, we had the last quarter net gain of NOK 4 million related to the currency positions. We have some funds in the euro account and also some Euro-NOK future contracts to hedge the currency risk. And year-to-date, we had a net gain of close to NOK 10 million from these positions. So these are positive contributions to the total P&L.
By the end of the third quarter, we had a total cash, as Carlos mentioned, of NOK 469 million or roughly USD 43 million. So this gives a fairly comfortable funding position, and we have an expected financial runway to the first half of 2024. This is the same guidance as we have been giving for quite some time now.
Looking ahead, we do expect the operating expenses and the negative operating cash flow to increase somewhat. And this is consistent with the guidance we’re giving on the financial runway, so we can move to the next slide. We are here sharing a picture of how the operating cash flow has fluctuated quarter-by-quarter, and we will expect to see quarterly variations also going forward. And it’s the R&D expenses that really drives these changes. With further initiation of sites and patient recruitment in clinical trials with milestones reached in larger projects with some changes in the CMC development, the manufacturing costs and also other R&D expenses, there will be – we will continue to see variations. But largely speaking, we expect a somewhat higher level of costs going forward.
Yes. Then we have on the next slide, just a quarterly breakdown of the operating expenses. This is more as a support to analysts who will like to dig into the numbers. So we will not spend more time on that in this presentation.
With that, we move on to the next section, and I’ll leave the word back to Carlos.
Presenter Speech
Carlos de Sousa (Executives)
Thank you, Hans. So if we move to the next slide. We always like to also cover what has been some of the developments in the immuno-oncology space. And I think we would like to highlight 2 recent developments. One is – and this was very, very public during the ESMO Cancer Conference. In September, the increased focus from oncologists and pharma companies on the moving to earlier stages of treatment of these patients, what is called a neo-adjuvant treatment across different cancer indications.
At the conference, there were different results, probably, one of the most became very public and visible was in the study the niche 2 in colon and rectal cancer that was presented by the specialists that you see in the image where picking up on this waterfall graph, you can see that basically, there was a response in 95% of the patients in the specific study. So this, of course, is creating more and more excitement around treating patients earlier in particularly in melanoma, for instance, is to start treating patients before the primary tumor is removed. And this is also an area that we are, as a company, exploring more and discussing more internally because we see also that this is a stage of the treatment that would benefit more also from the entrant of a cancer vaccine like UV1.
The other part – the other news that we believe are positive for the overall space at the cancer vaccines. As everybody knows, the cancer vaccines have not been very popular for many years, but I think that is changing. It starts changing with the COVID vaccines, raising the awareness of the vaccines in general. The big developments with Moderna and BioNTech thereto although they produced COVID vaccines, then they could do it in a fast way because they have more than 10 years of experience working with cancer vaccines using simotechnology. So this became now even more coming to the mainstream and more public with the recent deal that Merck exercised the option that they had with Moderna.
And also with BioNTech coming more to the market says that they expect the cancer vaccine to be out by 2030. This way we see this as positive in the sense of raising awareness of cancer vaccines. It’s not a direct competitor to Ultimovacs. These are what we call personalized vaccines, but of course, it’s always a good development, and we expect if data is positive to even be out on the market before they do. But anyway, very, very positive developments that we see in the overall space that are also supportive of the work we are doing.
So – but let’s talk about the month ahead. If we move to the next slide, yes, we have been, as a company, been delivering on our promises, a very, very consistently. But of course, it’s in the top of everybody’s mind in the next 6 months to 9 months when we are going to have the reading have the INITIUM in NIPU and that we expect as already several times mentioned during the first half of 2023. And of course, these are very exciting times. We, of course, if the data is positive, this will be revolutionary for us as a company, but also for the space overall because this will be the universal cancer vaccine, really, if the data positive showing in a comparative randomized study that cancer vaccines have a role in treating cancer patients. If the data is positive, as you can imagine, and we have been very public about that. On one hand, we will be meeting with the authorities, presenting the data, discussing the next steps. If the data is very positive, considered with them if there is room for a conditional or accelerated approval.
And on the other hand, we have – as you know, we have been told that we’re continuing in regular communication with big pharma companies that could be strategic partners in licensing UV1. And of course, these contracts in the back of positive data will accelerate. We see a big number of companies that – with positive data could be interested in taking on UV1. And we see this as positive not only for our investors, but also for patients. As a company, we are currently prepared to with positive data to move into 1 or 2 Phase III studies, but a large pharma company, of course, will have all the pieces in place for them to initiate multiple Phase III indications in different cancer types. So that will be, of course, a great value also for patients.
So very exciting times, and we are also now in preparation also for this data continue to putting a lot of emphasis on raising awareness of the company in medical conferences was extremely rewarding to get a presentation at the SMR conference in the main plenary session. But in addition to the medical community, we continue talking with pharma companies, and we are also increasing substantially the contact and reason awareness among investors and particularly specialist investors in other – the rest of Europe and also in the U.S. and that is going to be really a lot of the focus as part of the team is in expanding those contacts and bring awareness of Ultimovacs and what we do and the short to come data to these specialist investors. And of course, then we will have the other studies coming later on, and we will be providing you with an updated guidance with the Q4 2022 report.
So if we move to the next slide before we move to the Q&A. Basically, I just wanted to take the opportunity to thank the team. They have been doing a great, great job have making sure that we continue enrolling patients, really working on the data and getting this exposure medical conferences very actively working in the background doing a lot of these other activities that are not so visible like developing a commercial process for the product, preclinical studies, all these mechanistic studies that data is very positive and also the emphasis in raising awareness of the company.
So a big thank to the team, but also, of course, to all of you that continue to support us. We ensure that we have been delivering. We have these exciting period of time coming just around the corner. We continue to have a good – overall a good patient enrollment. The positive data to what we’ve been showing so far in the 103 study is very encouraging. And of course, in the more we – I talk with colleagues are the CEOs and other biotech companies and with advisers. We see that we are in a very good place in terms of our cash position that allows us to be focusing on the business without having to face the big hurdles of trying to finance the company in these very volatile times.
So with that, I want to thank you – all of you for the time you gave us to present the company for all your support, and we will move now to the Q&A.
Answer
Hans Eid (Executives)
Okay. Thank you, Carlos. We have received quite a few questions, and we may start with a couple of questions related to the UV1-103 trial. And I think Jens will be they want to answer those. The first one, what is the reason for 8 patients in UV1-103 missing PD-L1 status?
Answer
Jens Bjørheim (Executives)
So the reason for that is that when you try to collect tissue or biopsies from the patients, sometimes it’s not possible or the quality of such species are not good enough. So we actually do have information from 22 patients, and the last 8 are missing due to this.
Answer
Hans Eid (Executives)
Thanks, Jens. Then another question related to comparative data. The question is considering the differences in patient populations in UV1-103 and KEYNOTE-006 that you talked about, wouldn’t it be more accurate to compare KEYNOTE-006 results to the stage 4 patients from UV1-103?
Answer
Jens Bjørheim (Executives)
Well, so it’s never very good science to compare different trials. So as long as they are not conducted head-to-head you will always just get an indication. So the reason why we are presenting data from the KEYNOTE-006 trial is that this is the registration trial for pembrolizumab, and we think it’s valuable that the audience see the results for pembrolizumab alone. There are no trials that cover the same patient population as we do – since this is not a strong signs from the start, we do not want to go into subgroups and try to identify patients in our trial and compare them with specific patients in other trials.
So this is just to give an indication of the safety signals in our trial. I just also want to emphasize that we do think one of the most interesting efficacy signals in our trial is the number of complete responders. So we see really a push from stable disease and partial responses toward complete responses, which we saw in 33% of the patients. And now there’s only a few months or half a year until we will have results from our randomized trial. And in that position, we can discuss further the efficacy with UV1 on top of CPIs.
Answer
Hans Eid (Executives)
Thank you, Jens. Another question to you. You have done nice work with the PD-L1 biomarker to support the efficacy and overall universal approach. Does this translate outside of this trial and have a broader implication?
Answer
Jens Bjørheim (Executives)
Yes. So I also am curious about that. So the interesting thing here is that, remember, when you are using the CPIs, you are, in a way, even if that is very not maybe not very scientific to say it that way, but you are opening the tumor for the pre-existing immune system. So in some patients, they will have a sufficient T cell repertoire to kill off the can tumor to push the patient into a complete response. In other patients they do not have the sufficient number and quality of T cells that can help them into a complete response. So our thinking is that when you add a T cell that can be recognized tumors in all patients in the indication, telomerase is expressed in all melanoma patients, for example.
We expect that the immune system will be relevant for more patients. So also in those patients with a low PD-L1 indicating to some extent that they have fewer relevant T cells because then the tumor doesn’t need to protect itself with PD-L1. Also in those patients, we see good efficacy when we add the vaccine on top. Remember that this is only a few patients, but we will follow up on this in this indication and also in other indications. It would be very good if we could add a general vaccine on top of CPIs, also have a possibility to treat this hard-to-treat patients in the future.
Answer
Carlos de Sousa (Executives)
And if I can just make an additional comment. As we inform all of you, we have this extension study to the INITIUM where we are going to be in a more controlled way, really make all these collection of samples to do further examination. And of course, one of them is going to be the PD-L1 expression. So as that part of that extension study progresses and later next year, we will have additional more data. But this is, we believe this is a very exciting finding. It’s a small group of patients. But as Jens mentioned, shows that maybe patients that normally wouldn’t respond to pembrolizumab will respond with the addition of UV1.
And this is more relevant in some other indications where the PD-L1 expression in reality defines which treatment the patients are going to receive. Like for instance, in non-small cell lung cancer, if the patients are low expressers of PD-L1, they cannot just receive pembrolizumab alone, they have to add chemotherapy. So this is areas where we see that as we collect more information, it can be very exciting to see if we can expand the pool of patients that will benefit of adding UV1 to the checkpoint inhibitor.
Answer
Hans Eid (Executives)
Thanks, Carlos and Jens. Next question. We have seen very good survival data. How long do you anticipate you will track this? And how long do you believe the vaccine lasts in patients?
Answer
Jens Bjørheim (Executives)
Well, as you know, we have conducted 3 Phase I trials in the early days of the company’s history. And we follow those patients for the immune responses we induced in those patients, and we see immune responses after 7 years. It doesn’t mean that it stops at 7 years, but we will continue to follow these patients. But after 7 years, the immune response, T cells that can recognize telomerase are still there in the patients. We also follow these patients for overall survival up until 10 years, and we also follow long time overall survival in the other clinical trials we are part of our conducting. So this is the most important endpoint of course, and that can give the patients a long life. And this plateau, as we have discussed earlier in this presentation is very important, and we would like to understand how this develops over the next years in our trials.
Answer
Hans Eid (Executives)
Thanks, Jens. Moving on, we have a couple of questions related to the INITIUM trial. There are 2 quite similar questions, so you can probably both, yes. And the first one, INITIUM is often compared to CheckMate-067. Are there other and more recent studies that have come up with data for the nivo-ipi combination. And also another slightly broader question, do you know other comparable studies we should know how that can be relevant to INITIUM?
Answer
Jens Bjørheim (Executives)
So the reason – when you want to plan to start a randomized trial, you need to have some kind of idea how the drugs will work in patients. And at the time we started to plan for the INITIUM trial, the CheckMate-067 trial was the relevant trial and still is for the combination of ipi/nivo treatment. So this trial wasn’t necessary to plan for the statistics in the INITIUM trial. Other than that, when the INITIUM trial has started, of course, treatment with ipi and nivo may have developed over the last years. So when doctors get more experience with drugs, they become more aware of side effects that can occur other treatment of patients can improve, et cetera. So we are not dependent on the results from the CheckMate-067 trial, where the median PFS is 11.5 months.
We have, as we have discussed earlier, this so-called hazard ratio endpoint. So it’s not important if the control arm is identical to what was seen in the CheckMate 067, it’s the ratio between those 2 curves in the couple of that will be the endpoint in the INITIUM trial. When it comes to other trial, I guess the CheckMates 5 to 11 trial is very interesting where they have flipped the dose with a lower dose of ipi and a high dose of nivolumab. This is not an indication, and we do not have any knowledge that this will be approved indication for the combination of ipi/nivo. But nevertheless, it’s interesting results because the safety is lower when you have a lower dose of ipilimumab in that study.
Answer
Hans Eid (Executives)
Thanks, Jens. Another question related to INITIUM. Who registers relapses in melanoma/INITIUM? And how long does it take from patients have a relapse until this is registered in relevant systems?
Answer
Carlos de Sousa (Executives)
So I would not like to disclose the name, but it is a professional third-party company that is working with the so-called independent review. So what happens is that when the images are taken at the hospital, they will be sent to this third party and if they will be evaluated by radiologists in that company and scored. All the pictures from the hospitals will be sent and the – the results are the – the results obtained by this company are the numbers that will be used in the primary endpoint of the study. So there is a third-party collaborator that is – that are looking at the pictures from the study, and they will score all of the pictures. And when 70 endpoints is reached death and these pictures taken together and there will be a readout of the study. Of course, there is some lag in the system, meaning that it takes some time to transfer pictures from the local hospitals to the central institution, but this is a lag period that usually is very small and also towards the end of the study, there are a little difference between picture taken and a readout of the pictures by this third-party collaborator.
Answer
Jens Bjørheim (Executives)
I would like just to comment here because we get several times this question. I think there is some misunderstanding. So I would like to make it clear that we, as a company, it doesn’t matter for the results, how many events are so far when the 70 events are reached, the contract research organization needs to clean up the data. And we don’t – we are not exposed to the results. When the CRO is ready and cleaned all the data, then you would say, okay, we are ready to present the data to the company. And that is the time where the company is exposed to the data and we know at that time how many progressions are on each – in each arm.
So that’s the time when then shortly after this, we will inform the market. So again, the important part is the number of progressions after we reach 70 events. And again, only when the CRO has completed the cleanup of the data and all the images, then they inform the company about the results. So to be clear, we don’t know what are the results quite honestly, at the moment, no one knows because they have to collect the data, and this is only measured after the 70 events. So it’s just to be clear that the company will be exposed to the data, what was the results. And then at that time, soon after that, we will inform the market.
Answer
Hans Eid (Executives)
Okay. Thanks. Moving on to DOVACC enrollment. We have had some different questions that are more or less the same. So think will be captured in the following all of these. What is the primary reason for DOVACC enrolling patients at a slower pace than the rest of the Phase II trials? You also mentioned that new centers have been activated during the third quarter. Could we expect these centers starting to work with patients during Q4? And related to this, we also have the questions. Having implemented any initiatives to improve recruitment in DOVACC?
Answer
Jens Bjørheim (Executives)
Yes. So during the pandemic, we saw that recruiting patients in already open trials, maybe I shouldn’t use the word easy, but it was good. It was – we were happy with the enrollment of patients. It was more difficult to open new trials and open new sites. And this is due to negotiation around contracts, discussion about setup of the study at different hospitals, et cetera. And also different hospitals had some different prioritization during the COVID epidemic. This has changed over the summer and during autumn. So several new sites are now open in this trial. We have discussed this trial in different meetings with all the parties that participate in the study, and there is no competing standard of care that makes this study less attractive, even if it has recruited slower than we expected from the start.
We do not see any issues related to that. So we expect enrollment of patients to increase over the next months. Also, maybe a bit technical, but when patients are in screening in this trial as of now. But as you might remember from the inclusion in this study, the patients are on chemotherapy. And if they respond to that chemotherapy, they can be included in the study when they are finished with chemotherapy. So quite a few patients might have a response as of now, but they need to complete their chemotherapy treatment before they can be enrolled in the study. And therefore, it could take some time between screening of patients and actually enrollment in the study. But we are on the – there and discuss this with the investigators and other parties in the study and expect this to go faster over the next period of time.
Answer
Carlos de Sousa (Executives)
But again, I would like to make a comment here for clarification. These studies, the DOVACC study and some of the other studies are what is called investigator-initiated study. So we are not the ones responsible for running the clinical trial. We support, we provide UV1, but the coordination is done by the centers. This is totally different than the situation we had with INITIUM. In INITIUM and the team did a great job because we, as a company, could be in touch with investigators. For instance, Jens and the clinical operations team, a lot of times, were on the phone with these centers at midnight because these were in the West Coast in the U.S. So as a company that we are allowed to be in touch with the centers because it’s our run study.
In these type of studies like DOVACC and NIPU, LUNGVAC, we as a company, are not even allowed to be in touch with the investigators. So we – as a company, we have a much limited scope of activities we can do to support. The only thing we do is we are in touch with the investigators. We offer our support. But in reality, we cannot be – we are not even allowed to be involved in the operations, the running of the study. This is the responsibility have the lead investigators in the lead centers. So that, we are clear in terms of the difference between these type of studies.
Answer
Hans Eid (Executives)
Thanks. Then we have a question related to TET. And I guess this goes to you, Carlos. When will you inform more about the TET-platform in the future? Will there be an UV2 in combination with the TET-platform?
Answer
Carlos de Sousa (Executives)
Well, thanks for the question. We get – we get a met several times. So let me start by saying we are – we have different projects going with TET in terms of CMC, preclinical is absolutely natural. But as I mentioned several times, we also have several patents being reviewed. So we expect to be able to be more public and more tell more details about this during next year. And this is going to be dependent when the patents are granted when we have results from some of these studies that we are running at the moment. So we will definitely keep you informed, but will be sometime during 2023.
And then in terms of the question about what – which product at the moment, we are collecting this data. Of course, we also have the TENDU studies running. Then I think the great excitement to the potential for TET is that – the TET-platform is that we can derive different products from this technology for our own pipeline, but also to enter into collaborations with other companies that require a quite innovative adjuvant technology that is what is TET is, is a very innovative adjuvant technology, a very important component of any vaccine.
Answer
Hans Eid (Executives)
Thanks, Carlos. Then I think this may be the last question today. Does your cash runway include potential initiation of a Phase III in melanoma and for mesothelioma after INITIUM and NIPU? I’m happy to give – this answer, and then we should probably also put this into a strategic perspective, what are sort of the plans following Phase II readouts. But I can quickly address very specifically the cash runway. When we have the readout of the Phase II trials, it will, of course, be important for the development – further development to the one to move quickly into prepared in the next phase. So activities such as assuming positive data, dialogue with regulatory authorities, preparing for a Phase III trial.
Of course, we have anticipated such activities in the cash runway, we have guided on. There will be some significant activities related to that. It’s very different of doing some preparational activities compared to running the full trial because the cost is, of course, very different. Phase III trials, they have a significantly higher number of patients – so it’s a very different story, a full funding of our Phase III trial. So that will need separate funding if that should be made, but this should be put into sort of a strategic context of how do we think about proceeding after the Phase II readout. So maybe you, Carlos, would like to elaborate on that?
Answer
Carlos de Sousa (Executives)
Sure. Again, to reinforce what Hans just said, no, the funding of a full Phase III study, it’s not. These are totally different values. And I think we were clear about that. But as Hans says, what we will do is starting this preparation in terms of regulatory, CMC and of course, all the interactions with potential partners, that also will value all these preparations that we will be doing. So we will do as much as we can, and we’ll be prepared, but no, running truly, running a Phase III study will be require additional funding. And – but this would be, of course, if we need to raise capital to run a Phase III, is because we had positive Phase II. What is a totally different place to be? And this means, of course, that we had positive studies and will be a lot of excitement around the data.
Answer
Hans Eid (Executives)
Thank you, Carlos. Then there are no more questions today. Thanks for all the questions.
Answer
Carlos de Sousa (Executives)
Okay. So if that is the case, I want again to thank Jens and Hans for being here, presenting and, of course, to all of you for your support and for taking the time to listen to us. And again, you can send any questions to Anne, our Investor Relations Director that will be then happy to answer as many as possible. So again, thank you, everybody, and have a good rest of the day.
25 Likes
Kudos
Sitatet over er fra Bjørheim fra 7:42 i Q3 presentasjonen. Sløvt nok hadde jeg ikke fått med meg denne forskjellen i pasientgruppene ift. referansestudien, før presentasjonen. Det er jo såpass stor forskjell på stage IV og IIIC melanoma (f.eks. hvis man søker opp overlevelse på indikasjonen) at det vil overraske meg sterkt om det ikke har vært tydelig kommunisert fra selskapet tidligere. Noen som følger nyhetstrømmen fra selskapet tett som kan bekrefte?
Som polygon påpeker under. Stage3 er bred, med 4 substages. (og Tekk hadde en kilde på stage3 survival så la til den)
- Stage IIIA. The 5-year survival rate is around 78%. The 10-year survival rate is 68%.
- Stage IIIB. The 5-year survival rate is around 59%. The 10-year survival rate is around 43%.
- Stage IIIC. The 5-year survival rate is around 40%. The 10-year survival rate is around 24%.
Tenkte grafen var fin da den så godt viser forskjellen, og alvoret grovt sett i hva slags kreft hvert stadie innebærer.
3 Likes
Dette har blitt sagt og skrevet mange ganger tidligere. Ganske konsekvent.
Men ref grafen til @Sjakk , så er det stor forskjell på stadiene innenfor stage 3 også, som ikke gjør forskjellen melllm 3 og 4 i U sin studie så stor.
Takk Polygon, forventet det, skal gå tilbake å sjekke tidligere presentasjoner. Da er det vel bare incoming data-risiko som gjør at jeg nå fanger opp informasjonen 
Kan man forvente lignende forskjeller som på 5-års overlevelese (jmf utklippet til @Sjakk over) når det gjelder f eks respons rate? Da snakker jeg Pembro uten UV1, forskjellen på stage IV og IIIc. Og da tenker jeg helt generelt uten å ta hensyn til den spesifikke informasjon vi har om PD-L1 nivå og andre biomarkører.
EDIT, legger til overlevelse Melanoma fra nett (Sjakk sin figur differensierte ikke på undergruppene til III):
- Stage IIIC. The 5-year survival rate is around 40%. The 10-year survival rate is around 24%.
- Stage IV. The 5-year survival rate is around 15% to 20%. The 10-year survival rate is 10% to 15%. This rate is higher if the cancer has spread only to the skin or distant lymph nodes and not to vital organs.
1 Like
Må tydeligvis ha blandet/husket feil. Tridde det var motsatt, at ultimo hadde flere i fase 4. Dette endrer iallfall min risikovilje.
Om man blander inn den siste nyheten mhp pdl 1 status, den går vel motsatt vei, dvs i UV1 sin favør?
Ja, det er riktig, biomarkørene går i UV1 sin favør, i motsetning til sykdomstilstanden som altså går i UV1 sin disfavør når man sammenligner direkte med Keynote-006. Derfor jeg spesifiserte spørsmålet mitt til å gjelde for Maligna behandlet med Pembro (uten UV1) generelt, uten hensyn til biomarkører. Jeg kjenner ikke forskningslitteraturen godt, og svaret på spørsmålene mine er i alle fall ikke super-enkelt tilgjengelig via Google søk.