Good morning, everyone, and welcome to the Q4 results presentation for Nordic Nanovector. My name is Erik Skullerud. I'm the CEO since five months back now, so this is my second quarterly presentation. Together with me today, I have two of my colleagues, Malene Brøndberg , CFO, that you will already be familiar with, and I also have a new colleague that I want to introduce to you, Sandra Jonsson, who is our new COO. So the three of us will be entertaining you, hopefully today, and also having a good conversation hopefully. Last time that I was here was back in October, I believe. Little did we know then of different events that have happened in Q4 and also into Q1.
Honestly, a couple of weeks ago, I thought I was coming back to Norway at the back end of Omicron, only to find out a week ago that obviously the geopolitical landscape had changed, and we find ourselves in a new crisis. I just wanna take a moment to just think about and give a bit of good feelings down south towards our friends in Ukraine. I hope that this is a conflict that will not take too long. It doesn't look very good, but they should know our thoughts are with them. Before we jump into the presentation itself, some forward-looking statements that you are all familiar with.
Make sure you realize the aspirational nature of what we are about to say today, and that you familiarize yourself with those before investing in the company. As mentioned today, two of us will be presenting. Sandra, feel free to reach out to her after the presentation and get to know her somewhat. Malene will talk about the financials. I will talk about a business update first. Let's jump straight into it. In Q4, we spent a lot of time focusing in on PARADIGME, which is our primary priority. Today, we are reporting 106 patients, and we'll talk about this number a little bit more in detail in a bit.
As you will know, we changed our guidance early in January, to suggest that we are now getting the results of PARADIGME in the second half of this year. We maintain this guidance today, although, and you will see that in a moment, Omicron has hit us very hard. We did get questions on this already in December. We did say already back then that this was something that we were going to take our time to evaluate. We have done so, and you have seen the consequences, but we'll spend a little bit more time. Secondly, excuse me. We also did an emission now just after Christmas. With the new, timelines for PARADIGME, it became obvious to us that we needed to get in more and increased financing in order to reach the final, readout of the study itself.
We got about NOK 250 million, and let me already now say a big thank you to those of you that were part of investing at that time. As you will also know, we have an emission ongoing, and I know that there are certain question marks around this based on the geopolitical environment that we find ourselves in. But that being said, please keep in mind that when it comes to emissions like this and the specific Norwegian private placement associated with this is something that is weeks in the planning before you actually go out and execute it. On top of that, it is really important for us to think about all of our shareholders, not just the big ones. We also want this to be an opportunity for smaller shareholders.
As mentioned in Q4, we have also added two new people to our executive management team, Pierre Dodion, that you were introduced to in the R&D day back in November, and Sandra Jonsson, who is joining us as of the tenth of January, but was appointed back in December. In addition to that, we have a couple of other things that we have also announced and that you will be familiar with. Number one, we announced a collaboration with the HPP around better understanding the potential barriers to entry for radionuclide medicines in the global environment. This is important when it gets to our launch because that's gonna underpin the success of the launch itself. Finally, we announced a collaboration around CAR T together with the University of Pennsylvania, something that we are really excited about.
This is one of the foremost research, collaborative organizations in the world when it comes to cancer medicine. They have developed a unique, technology around CAR T, and as such, is a collaborator that we're very proud to be associated with. Back to PARADIGME. When it comes to PARADIGME itself, as mentioned back in November, we did already then see some early indications that this was going to potentially be a challenge for us. We mentioned already at the R&D Day that this was something we wanted to spend time on, better understand. We spent the whole of December, and especially the Christmas and New Year's period, diving into this analysis. I think we must have spoken to somewhere in the area of 30-40 different centers.
Myself, I've been on 20-25 of these calls. To better understand what was the impact on the ground, with regards to cancer treatment, hospital environments, and how that could affect our study. As such, we went out with new guidance in January, and this time we put a lot of effort on we wanted to be ahead of the wave. We wanted to be transparent and open to you around the impact that this has had on inclusion in PARADIGME. Hence, the guidance that we're giving today is the same that we gave, back in the beginning of January, so we did not get any new patients from then until today.
Again, we saw this coming, and I will describe exactly how we saw that in a little bit, but that was important to us to already back then go out with it. The good news is this situation is, as we can see now, starting to change. Let's spend a little bit of time on that. On the left-hand side of this slide, you will see targeted initiatives that we are putting in place either have been, are, or will be doing, as we speak. We spent a lot of time and efforts, and I mentioned this also in my Q3 presentation, on really segmenting and better understanding the different centers out there. Where are they on this journey? Are they the kind of centers that will, yeah, we're really interested, we are screening, and therefore we are including patients.
Are they on the journey or we're kind of sitting on the fence, we think that this is a good study, but we haven't found a patient. Or are they, we have other things to do. For those of you that are even involved in clinical studies, you know that all of these different types of centers exist in any study out there. About 70% of our centers are actively engaging, actively trying to find patients, actively trying to work with us. The last 30% is for us. They need to be in there because they have patients in the past, but they are not necessarily that active today.
The main countries as far as inclusion is concerned, and this is a question that we have gotten over and over again, and today I'm happy to relieve some of that, those questions are North America, U.K., Ireland, and Spain. As a Norwegian, I'm a bit disappointed to see that the Nordic countries is not on that list. I must be honest. Because when we look at the development of Betalutin, a lot of the early patients were included in Norway, in Denmark, in Sweden. For whatever reason, I'll get to that in a second, that is not happening today. I think it's fair to say that with Dr. Kolstad moving from Radiumhospitalet, one of our biggest supporters moved jobs, so to speak. We still have a great working relationship with him.
I'm going myself to meet with the Radiumhospitalet tomorrow, to meet the new principal investigator there. Our senior management staff is now going on a tour around the whole of Scandinavia in the next couple of weeks. Sandra will be doing this together with our MSLs. This is important to us. We're a Norwegian company with a Norwegian base and we should do better in Scandinavia from an inclusion point of view. That being said, I mentioned the guidance that we gave back in January. On the right-hand side of this slide, you can see how we monitor the study. All of those different parts, those filters, if you want, in the funnel are where we look at patients.
We know exactly how many patients are under consideration, how many have consented, how many are in early screening, and how many are in late screening. Back in December, we saw that the lower part or the upper part of this funnel started to thin out. There was less and less patients. We saw that there were still in the funnel some patients that also got included up to the sixth of January, seventh of January. The good news today, as when we look at this funnel, we have more patients in the upper echelon of this funnel than what we've ever had. I'm not just saying that to please you, but these are true numbers for us where we can see that this is going in a very good direction.
We have a lot of patients under consideration, partly because of initiatives such as Trialbee . You see on the left-hand side also, we have added one additional clinical scientist. This person is every time we get a patient under consideration, this patient is in direct contact with the center in question. And as such, we have a much better feeling for these patients now than what we did six months ago. Over and above the clinic itself, there are several pieces of the puzzle that we need to get right before we can eventually submit the file. We've spoken about the clinics, and we've gone on about how many patients are enrolled and what we need to do. Over and above that, it is the regulatory interaction itself. We have two interactions that we will do in the next four to six months.
One is coming up at the end now of Q1, which is with the FDA around our future phase III confirmatory study. This is around a discussion with them on what is going to happen and how is the study going to look like. Just as a reminder, we'll get back to this a little bit later, the PI3K inhibitors that have been taken off the market, several of these products did not do this interaction well. We do not wanna make the same mistake, and as such, those interactions are happening now. The second point with regards to the FDA is around production, manufacturing, supply chain. You heard from Lars back at the R&D day, and there is a reason for why we keep on talking about this. Without that part of the puzzle, we will also not be able to submit a file.
As such, getting that right and doing it upfront is really important. I'm really proud of the work that is being done in that field because we're making great strides in order to be ready, and we're fully on track in making that happen. That's one part or two parts. The third part, and we'll get back to that at the end of the presentation, is our strategy around partnerships. Again, a lot of work is happening, and I think some investors may think that this is a matter of just turning a switch. This is work that needs to happen and needs to happen over time. Especially with big pharma, strategies around how you partner is they will only go in once they see the data.
I would anticipate, and I think we should all anticipate, that until we have the data, the big pharma will not knock on our door and say, "We want to partner." That's not to say that we're not talking to them because we are, but it's not to say that they're gonna say, "We're gonna sign you up," until we actually have top-line results. Back a little bit to the manufacturing side of things because this is important. The first thing we need to do, and we have been working on in the last three years, is around the so-called PPQs. This is qualification around how our production process happens, a validation that we can do the same over and over and over again, and ensuring that that product process can go from clinical substance into commercialized sub-substance.
The second thing that we need to do is to take all of that information, categorize it, and put it into the BLA, into the file itself, and ensure that file is solid, that file can be used with the FDA. As mentioned, the first interaction that we have with the FDA specifically on manufacturing is gonna happen in June this year. So far, everything is on track. As far as I am concerned, I've seen several companies do this, we're ahead of the curve on this one. The team is doing an incredible job. Then when we get to launch, obviously it is to supply the market, but already now we're also thinking significantly about cost of goods, profitability. How can we streamline this process so that at the end of the day, the profitability of the company is ensured?
In that sense, we have in the last, I don't know how many quarterly reports talked about what happens before we submit. Today, I wanna talk a little bit more about what happens after we have the results. When we have the results, the first thing that will happen is that a lot of people in a lot of places will start analyzing. Already now, a lot of analysis is happening, but in order to make this happen, number one, and to fulfill our obligations, both on patients that are early in the study, patients that have progressed through the study, and patients that are all towards the end of the study, all of that data points, tens of thousands of data points needs to be analyzed.
Now, everything you see on this slide in gray is stuff that we cannot predict from a timeline point of view because it has to do with the nature and the quality and how good or bad the results are. In other words, when we give our first, "We hit the primary endpoint," that is when we can start predicting how long that process will be. Both from a data cleaning point of view, pulling the file together point of view, we need to see what the data is actually telling us. During the course of that time, we will request a so-called pre-BLA meeting with the FDA, and in that meeting, we'll have a conversation with them about the data package, the quality of the data package, and how that is according to what they expect from us.
Again, our expectation and all the interactions we've had so far is that we're doing the right thing, we have the right study in place, we've done the right statistics, and we're executing according to what they expect from us. That will be a very key moment for us, where we have that interaction, and we can then start the filing. As you know, due to the nature of our Fast Track, we can interact with the FDA on a continuous basis. Believe me, we're doing that as often as we possibly can. That is to ensure that we don't get any surprises during the course of this journey.
Once we get to the submission and the submission is done, the timelines become much clearer because when that happens, the FDA has two months to review the data, and then they will tell us either you get a priority review, which is six months, or you get a normal review, which the vast majority of these submissions actually get, and that is 10 months. The highest you will get with regards to the review time itself is 12 months, and then we'll be ready to launch. This is what this is gonna look like once we have gone through the motions of analysis, discussions, and review with the FDA. We're not just thinking about that. We're also thinking about the commitment that we have as an organization because of the approval route that we have taken with the FDA, the phase III confirmatory study.
Again, this is preliminary, what you see in front of you. It is second line rather than third line FL. It is a combination rather than single agent. Those are areas where this differs from what you have seen in third line. The market opportunity over here is also close to twice that of third line. We're talking about significant upside if or when we do this and go into second line. That is the discussion that we will have now with the FDA, towards the end of the first quarter to align around this design. Just to remind you, in NHL, which is our focus, our primary focus, this is still one of the largest unmet needs within cancer.
The fact that so many PI3K inhibitors are going out of the market makes that unmet need even more significant, especially in the patient group that we're talking about, and I'll get back to that in a second. Again, just to remind you, the clinical data that we have so far is extremely promising. You can see in the middle of the slide here, the two numbers that have been circled. This is the patient group that is the closest in the part A, the data that has already been published, to what we are doing in PARADIGME. This is kind of from a comparison point of view. Let me remind you, it's not exactly the same, but it's the closest that you get in the numbers that we or in the data that we have presented so far.
Let's dive into the competitive environment. I'm gonna show you three slides, because I get a lot of questions from investors on this. The first one is related to, and you've seen this before, but it's important to underline the patient population. On the, on the horizontal slide aside here, you see patients from left to right, those that are young, fit, and is available for more aggressive treatment, but also more toxic treatments. These are patients that constitutes approximately 25% of the total population in third line. In third line, equally, the right-hand side, the unfit, the elderly, and the frail patients, they constitute approximately 75% of the total patient population. These are the ones that we are after, and that's important to keep in mind.
Now, when you think about going from third line into second line, the combination treatment, then efficacy becomes much more important. Efficacy you will have seen in the Archer study. That's our first combination trial with rituximab, what we're looking to do also in the confirmatory phase III. Efficacy becomes more important, but again, half of that population in second line is elderly, frail, or they cannot have more aggressive therapy for whatever reason. That's the first thing that's important to keep in mind. You see a couple of X's on this slide. That is the three different PI3K inhibitors that have been pulled off the market. Those are no longer competitors. From a purely competitive intensity point of view, those are gone.
As such, we believe, we anticipate the competitive intensity in this marketplace to be significantly less when we enter than what it is today, because this slide also includes other treatments that would be launched ahead of when we get in there. This picture over the last three to four to five weeks have changed in our favor significantly. The second piece of questions that I'm getting on the competitive intensity is then not so much towards PI3K, although I'll touch upon copanlisib in a second, but it's related to the other two major groups of treatments. Number one, CAR T, number two, bispecific antibodies. With regards to CAR T, the most significant threat perceived by other investors is around efficacy. With regards to efficacy, yes, efficacy is impressive by CAR Ts. However, keep in mind the full profile of this group of treatments.
Approximately half, if you look at FL only of these patients, get what you call, the cytokine release syndrome. This is toxicity that is potentially deadly if not treated and not treated well, and you need a highly specialized unit in order to treat it. This is not for frail patients. This is not for elderly patients. When you look at bispecific antibodies, that same number of cytokine release syndrome is, approximately 38%, 35%-38%. It's less, but it's still significant toxicity. Now, let me qualify that because obviously bispecific antibodies you do not have in the market yet. We do not have so much clinical experience with it yet. We only can go by what is actually being shown in clinical studies so far, both phase I and phase II.
Again, efficacy is impressive. As such, we believe that those two product classes will be more for the fit population, more for the patients that can actually tolerate this. Those are younger patients and are patients that we will not be competing for anyway. The final point I would like to make is regards to copanlisib. Because copanlisib, we're getting a lot of questions on Accelerated Approval, how will copanlisib, if it gets a full approval, how will that affect our chances of getting Accelerated Approval? Now, keep in mind how they have designed their studies. Their studies are done, both CHRONOS-3 and CHRONOS-4, are done in patients that are sensitive to rituximab therapy. That is one of the exclusion criteria for the population that we are targeting.
In other words, first of all, from a competitive point of view, we don't believe that this is necessarily a big competitor. More importantly, our ability to get Accelerated Approval, we do not believe that that is going down as a consequence of them getting a final approval for that specific reason. We are targeting a different population than what they are. In that sense, let's talk a little bit about the positioning and what we will be bringing to market. Obviously, there are several dimensions to this that we're keeping a little bit under wraps because we don't wanna show our future competitors exactly what we'll be doing. From a top-line point of view, in third line, we are targeting elderly and frail patients.
We're targeting that with the value proposition of duration of response, a one-time only injection, and a manageable tolerability profile. Something which is unique in this marketplace, something that we can compete on, and we can sustain a competitive advantage. That is what we believe for third line. In second line, it becomes a combination proposition. What can we do when we combine Betalutin with rituximab? You have seen in preclinical data that there is a synergistic effect. In other words, we enhance the efficacy of rituximab even further, and you get the over-and-above effect from Betalutin. We have shown it in early clinical studies, in the Archer study, and that's the first comfort you should take in our ability to be successful also in this setting.
Finally, we're working now on looking at further patients, what could happen, what does happen once you get off Betalutin. We're looking into our own studies, what happens to patients that get off Betalutin and get rechallenged with rituximab. We're looking at that, and we're hoping in the next six to nine months to have a first-line analysis of it. But we're trying to build this value proposition to strengthen this value proposition in the face of also going into second line. We're thinking forwards here as well. The final part around Betalutin, and then I'll stop on Betalutin itself, is around the HPP collaboration. This collaboration, as I mentioned upfront, is intended to dampen barriers for entry.
For those of you that are truly interested in how you succeed in pharmaceutical marketing, this is the way to do it. Doing this upfront, I'm not gonna take any of the accountability for this. This was done way before my time. Other brains were thinking much better than mine on this. This is something that we are doing. In fact, we were one of the first to initiate this, but other big radiopharmaceutical companies have joined us on this journey. As such, companies that are launching pharmaceuticals in the radiopharmaceutical space now, they're paving the way for us if you want.
They're utilizing this going into the market, and we will learn together with them because this is a collaboration of sharing of data. We will understand exactly what it is gonna be taken to be successful in this marketplace. That takes me to the last slide which is related to Betalutin, and then we'll go into the rest of the pipeline for a couple of slides as well. What I wanna highlight with this is what we also presented back in November, December in our R&D day. We initially talked about Betalutin, the pipeline that we're trying to create of the product itself, but we also highlighted the four other assets that we have in the pipeline.
Two of which are now under collaboration, one with Orano Med, the Alpha37, also a radioimmunotherapy, and our CAR- T product. Just a couple of pieces of news around what's going on in the other part of the pipeline as well. Because we are spending, as I mentioned last time, 80%-90% of our efforts, of our energy on Betalutin, but we also do find time to do a couple of other things. For Humalutin, we have submitted a paper, preclinical, but this is together with a PARP inhibitor. For those of you that are familiar with PARP inhibitors, you will know that these are big in breast cancer, in ovarian cancer, and some of the more promising oncology therapies out there.
We've submitted a paper together with olaparib, a combination treatment, preclinical, to show the dual efficacy of the two. For Alpha37, we're also progressing very nicely with our partner. Right now we're waiting for answers from the FDA around production, early stage production, GMP, and manufacturing for that specific molecule. Again, we are targeting an IND together with Orano Med, and we're getting the next milestone for us internally towards the end of this month also there. The final piece is related to Humalutin and to CAR-T. For Humalutin, we are in the midst of choosing the final candidate that we'll bring forward. This is as you know, this is a clean antibody, and here we're looking at partly NHL again or potentially immunological disease.
We spent the last few weeks talking to opinion leaders around Europe on where's the best opportunity, how can we do this the best, and we're collating those results as we speak. Finally, on CAR-T, the program has now been started, so that is work in progress, and we're expecting further announcements from that towards the end of this calendar year. Just a couple of words on CAR-T and then I'll speak a bit about partnering as well. On the CAR-T collaboration, as I said in the beginning, we're obviously very excited about this. This is a collaboration that we believe for future reference will be an extremely important one for us.
We also believe that this will be the next generation CAR-T because of the way that we do this with them and the technology behind it. If things go the way that we hope, if things go the way that we aspire, you'll see a different way of both mechanism and efficacy, and safety than what we've seen with previous generations of CAR-T therapies. That brings me to the last slide before I let Malene take over with the finances, and this is around our partnering strategy. A lot of questions are coming from investors around how we do partnering. As I mentioned in my last presentation to several of you, we have one person internally. In fact, we have several that are working basically night and day on the partnering itself.
The conversations that we're having are falling into three different categories. One is around commercialization for Betalutin. This is about North America, it's around Far East. It's really how do we make a success of Betalutin around the globe. The second one is falling into considerations around, let's call it mid-stage pipeline assets. This is around Humalutin, it's around Alpha 37, and to some extent even our earlier stage assets, where it's more around how do we bring this into humans and how do we bring this through the clinical development cycle. The last one is the CAR-T example, where we're forming alliances, collaborations, with other scientists in order to start scraping the surface and really understanding what an asset could look like. This is what we're spending time on. We have several conversations ongoing with different parties as we speak.
As I said, with regards to commercialization, I would not expect a big partner until we get to the top-line results. For the other two, there is definitely a possibility that we may get traction. I think with that, I'll let Malene take over and talk about the finances, and then I'll come and summarize. Malene.
Will you hand that over to me?
I will do that.
Thank you. Okay. Good morning as well from me. Let's see how this works now. No, that was the other way. Fantastic. Here we go. Okay. As you can see, the cost was NOK 133 in Q4. As you can see here, the net cash position from the operating activities ended up around 89 NOK million. What's more important is, of course, if you look at the spending that we're going into now here in Q1, because you could see at the end of the year we had NOK 278 million. Then you can ask, why did you go out and take some money in at that point?
Because that's quite a lot of cash. With the new cash that we had, the NOK 250 gross, which boils down to roughly after we paid the help, we had roughly NOK 233. Add those two numbers up, you could say that it is a pretty good cash position, and it is a pretty good cash position. What you can't see and what you see when you see our Q1 numbers is that we had a pretty good outgoing. I would say it's not good, of course, to have a good outgoing, but we had an outgoing, or will have in Q1, which is roughly around NOK 160. We had last year NOK 130 approximately.
The reason why we have this much more going out this year in the Q1 is because we had a change order, which is part of the business when you do a work with the suppliers like Icon, which is our CRO. When you reach a milestone, you have to pay out, and that's why. You can see that the cash position will change dramatically when we come to the Q1. Just if anyone wonders why did we actually go out at that point, and of course, unfortunately, we have, as you know, to extend the timeline. When you look and that's why we had to go when we went.
Of course, it wasn't an ideal situation when it came to the market, but unfortunately, that's the nature of the business and the market. When it comes to the cost, for the Q1, we will probably look around the NOK 120 mark. Hopefully that will give some explanations into why, if we look at the good cash position, what's actually going to happen with that cash position. If we look at the repair issue, which we have ongoing, we've also got a lot of questions. Why do you do this repair issue? Why didn't you just cancel it? Well, the repair issue, it wasn't something that we just started yesterday. It's a long process.
When we did the private placement and completed that, as you know, on the nineteenth of January, we actually at that stage started the prospectus update of the prospectus, and that takes more than a month to get that through. It takes roughly six weeks to get that through, yeah, with the FSA authorities here in Norway. It is a quite costly process. So of course, we could have said, "Okay, now we're going to cancel the repair," because we are right now under the 14. But on the other hand, as Erik just said, we want to give everyone a chance. So if we had gone off and they, we would.
There was still an opportunity to come in, and since we have already spent the cost and a lot of time, I would say there's a lot of time going into this planning and doing the prospectus. That's why we continued, mostly because we want to give everyone the same opportunity. It is running until the eleventh of March, and of course, with everything else, as also Erik said, going on in the world, let's see where we end with that. With that, I think I'll hand it back to you, Erik.
If I would always be as efficient in presenting as you, Malene Brønborg. I want to just leave you with this slide. I'm not going to spend a lot of time on talking about it, because you've seen it before. It's kind of in a nutshell what it is that we want to leave you with. Our asset Betalutin, which we spend days and nights in supporting, promoting, making sure that we do the best job for bringing that to market, is our top priority, and it remains our top priority. There is more to Nanovector than just Betalutin. There's also other assets that we're working on and that we're trying to bring through into clinical development and eventually into patients.
Although Betalutin on its own could be a pipeline for us, we're also looking at other attack points based on the science around CD37. I didn't mention CD37 in my presentation, but I still am just as excited, even more excited today than what I was when I joined the company, because I did not know that there was a CAR-T going as I joined, and I think that adding to the wider pipeline is a significant step forward for us. As Malene has said, from a financing point of view, we have money well into 2023. We have money beyond the readout of the top-line results for PARADIGME, and we are obviously extremely excited about 2022. This is for us the year where push comes to shove.
This is when we will see our little baby walk for the first time, and hopefully those results, and we believe that those results will be really, really good ones. With that, let's end the presentation. I believe that we have some time for questions, so let's go for those. Anyone in the room first before we open the online questions? There does not seem to be any questions in the room. Do we have any online questions?
Yes. Good morning. We have a number of questions online. We'll start with some questions, if we may, around PARADIGME. We have a number of overlapping questions regarding PARADIGME. The first one of those is a question as to why you do not report more often how many patients are included in the study.
Let me just remind you of what we have done in the last quarter-ish. We spoke to you on, if I'm not completely wrong, on what was it? The seventeenth of November, which was Q3. We then reported a number. We had another R&D presentation, R&D day on the thirtieth, where we reported a number, and we had a sixth of January where we reported a number, and today we're reporting a number. I don't see how we can do it more often than that, to be honest. That to me is as often as we can get. That's number one. Number two, as I think you can see, this isn't something where we just turn a switch and numbers flow into the study. This is a rare disease.
This is a rare disease, and patients are not that easy to find. On those bases, our estimation is that quarterly reporting have been often enough. That being said, we have made an exception through the course of the last quarter with four interactions, and I hope that is sufficient.
Thank you. Next follow-up question on PARADIGME is around can you offer any further explanation as to why the recruitment rate seems to have stopped since early January when you last reported?
It's a very good question. As I mentioned, my own Christmas-New Year holiday was spent on pondering and researching that question. For anyone out there that have family that are in hospital for whatever reason and have been to a hospital of late, you will have seen the chaos that is in the hospitals. Whether that is in Norway, Sweden, U.S., Greece, Turkey, Australia, Italy, Spain, Germany, and I've spoken to hospitals in all of these countries in the last six weeks. It's the same thing that you see. Although we're going out of Omicron in Norway and in Sweden, in Denmark, in Switzerland at this stage, in Germany they're not yet. In Spain they're not yet, although they're saying they may get out of it towards the end of Spain.
The point is, for the patients that are not severely lethally ill and have immune deficiency, which these patients have, they're not coming to the hospital. They're not being enrolled in studies. I mentioned this in the R&D presentation that we had back in November. 60% less patients have been included in studies in the U.K. in 2021 than those that were in 2020. That being said, what we have also seen with Omicron specifically is that the message that we heard from the experts when Omicron hit back in November, and it was iterated throughout December and into January, was that this strain is not gonna be as sensitive to the vaccines. Another driver for why patients do not come into hospitals.
The final driver is just that hospitals, and this is in my mind the biggest driver for the chaos that we're seeing at the moment, patients that have been not going to hospitals for whatever reasons are now coming back, but they're crash landing into intensive care and into severe care, which means that those beds that could be used for cancer treatment are actually being taken by severely deadly ill patients, hence why you also see the chaos in the hospitals. It is no longer Omicron specifically related, but this is the backlog that we have, by the way, expected, for the last two years of patients coming into the system. That to me are the three key drivers for why you have not seen inclusion as such in the study.
As I said, over the last two to three weeks, we have seen a lot of patients starting to go into consideration. We have started to see them go into screening. This to me is a leading indicator for that this is a situation that very likely, and let's hope that there's no further strains that we'll get, but it's very likely, we can see the light at the end of the tunnel.
Thank you. The next couple of related questions are firstly, when do you expect the enrollment rate for PARADIGME to pick up again? Following up on that, do you think the guidance of readout in 2022 is still achievable when the recruitment rate has been so slow?
Let me tackle the second part first. Yes, we do. Again, assuming that we don't get another Omicron or another strain that we even have more issues with, number one. Number two, when are we expecting them to pick up again? I would say something in the area of the next four to six weeks, we should see this trend turn.
Thank you. A further question on PARADIGME is regarding whether or not you can give any more specific numbers around the number of patients under consideration or in enrollment at this stage, versus historically.
I can say that, like I said in my presentation, the number that we see now is higher than at least what I have ever seen from an enrollment and from a consideration and early stage screening. I have not seen this number since I joined, and from what I've understood from others in the company as well, these are very high at the moment. I don't wanna go out with specific numbers and I'll tell you the reason why. Patients that are going into enrollment, and the funnel is there for a reason because the numbers that go into the early stages of the funnel, they come down. Some patients come in and then they go back out again. They don't make it all the way to actual enrollment.
You know, in the part of Norway that I come from, directly translated, these numbers are, and this is where the quote, "It goes like sour milk in a kitten." It basically goes. It swallows and then it comes back up again. This is how we would describe what's happening in these numbers. Hence, for us to go out and say the number early stage is 15, and I just made that up by the way, this is not the real number. The next week it would be 12, and then it goes down to two, and then it goes back up again. These numbers are changing on a continuous basis, hence why we don't go out with them. We would confuse, sorry, my language, the hell out of you if we would do this.
We'd much rather be in a safe place where when we are saying this is the number, you know that you can have confidence in it.
Thank you. Just one further question, around PARADIGME, which is how long does it take on average from the top enrollment stage to the bottom? I.e., how long does it take for a patient to go from screening to dosed?
Very individual, but I think I mentioned this before, approximately two months from when we first see that patient until they are finally enrolled. The delta and the difference between numbers here is significant.
Thank you. We now have a series of questions regarding the private placement. The first of those is, given the current share price is trading below 14 NOK, and the cost of the private placement, can you not save cost by canceling the offering at this stage?
I wish. It's not the way the financial system works, unfortunately. There is also a legal obligation that when you go and do a private placement, you have to treat all shareholders equal. You can make a decision not to do so. We're of the belief that we should treat all shareholders the same, big and small. By the way, when I started, one of the first few questions that I got, and I believe even this was in one of the Radforsk discussions, it could have been somewhere else, but I got several questions related to the same. Why have you guys always prioritized the bigger investors and not the small investors? It's a little bit of damned if you do and damned if you don't. This time around, we decided we wanna treat all of you in the same way.
Geopolitical, its issues is something that we can't control. I dare to say that we find ourselves in the situation that we are due to those specific issues. As Malene alluded to in the beginning of her presentation, this isn't something that you turn a switch and then it just goes within 24 hours. There's a lot of time and commitment that is put into this. Bottom line is we couldn't have saved the money because that is something you have to pay upfront when you do this, and that is just the way the financial system works.
Thank you. Just moving on to a rather broader question now, which is a question as to what is the level of interest for radioligand therapy and Betalutin specifically, among both doctors treating patients and patients themselves?
If anyone read was it Fierce Pharma yesterday, there was an article related to Novartis's PSMA molecule where they said. It's very much along what we have also said about Betalutin the whole time. The interest is definitely there. The headline of this specific article was the following. "Novartis's drug gets increasing confidence and commitment from oncologists, but supply issues and something else needs to be overcome." Basically, what they were saying was that out of X number of oncologist asks, the faith in the product is tremendous. This is what they're saying, Novartis have to make sure that they get it right with regards to supply chain, distribution, and getting this product to us.
In other words, what we have picked up, by the way, together with them around the whole HPP organization, because they are, as you can understand, one of the other companies that are supporting this rollout. That, over and above that, I would also underline from 2019, sorry, to 2021, you had four big radiopharmaceutical collaborations signed for the Western world, significantly more if you include also the East, the Asia, Southeast Asia, China, around radioimmunotherapy, and you see new companies popping up on a constant basis in this field. This is something that is definitely very interesting at the moment.
Thank you. We also have two or three questions around the Archer-1 study, which essentially ask whether you can give any further updates around Archer-1, and in particular of the seven patients enrolled in the study, can you give any specific updates on complete and partial responses, duration of response, how many patients are in remission, et cetera?
I think the last update we gave was at the R&D day where we said out of the seven patients, six had either complete or partial response, but none of them had gone into remission. That's the latest piece of information I have. I have not heard anything since then. Keep in mind that the patients in Archer-1 are now all going towards three years of follow-up. If this really holds true, this is a significant result that we're seeing in this study, although small and with all the caveats you should have for an early stage study, these results are impressive no matter how you look at it.
Thank you. Just as a reminder at this stage, if there are any further questions, please do submit them via the link on the company's website on the webcast link for today. The next question is a broad question which asks, "Why has Omicron hit you harder than the first COVID variant?
Very good question. I think there are a couple of reasons. First reason is probably the first strain. There was a lot of uncertainty what this even was, and it took time for the community to really figure out how to manage it and how to respond to it. Once they got their act together, we saw this for the second strain, if you want, the Delta variant. As soon as experts came out and said, "No worries, vaccine is there. This strain is also receptive to the vaccine." You saw that our recruitment numbers went through the roof. Omicron is a different story.
The same experts came out and said, "No, this time around, sorry, this is not as receptive, as sensitive to the vaccine." I think that lack of guidance, if you want, or that uncertainty is arguably one out of two main reasons for why Omicron has hit us harder. The second reason is the sheer backlog of patients that are coming in, as I mentioned earlier, crashing into intensive care, into severe care, and that are taking the seats, the beds for these patients. Those are the two reasons for why this has hit us more than the first strain.
Thank you. Then just lastly, we have one or two questions on the competitive positioning of Betalutin, which essentially ask whether you can add anything further with regards to the competitive positioning with respect to other classes of drugs, either currently on the market or in development. Again, you made some specific comments on copanlisib, but there are one or two questions asking whether there's any further information you can share around that particular drug and how it sits competitively versus Betalutin.
Let me take the second one first. With regards to copanlisib, I think one is the patient group that we are targeting, which is different, and that's important to keep in mind. Two, for copanlisib, and I would extrapolate this to any also future launch of PI3K, the fact that what we have seen in the last four to five weeks, with three products being withdrawn and one, umbralisib that have withdrawn their application for MZL, there is no doubt that this is gonna hurt the whole class, not just the products in question.
My assumption is that this is going to be seen as a class effect, and I also believe that irrespective of what happens with copanlisib, they are going to have a fair share of convincing to do with the scientific community around why these drugs should be used to begin with. I don't know that, but that would be my assumption based on what I've seen in the past. This is not something that doctors look kindly upon. With regards to the other classes, I mentioned the efficacy versus tolerability part. What I did not mention was the whole economic consideration.
If you work with the CAR- T, the efficacy, even if you get it to work, you're using a drug that costs approximately, in the U.S., before rebates, $450,000 just for the injection itself. If you on top of that take the number of days that you need to stay in the hospital, and if you assume that approximately half of these patients actually get the side effect of cytokine release syndrome, that is an enormous cost over and above. The last thing that I would like to highlight with CAR- T is, again, for those of you that are scientifically interested and are reading the New England Journal of Medicine, there were two articles just before Christmas related to CAR- T, but in DLBCL, large cell lymphoma, where the cytokine release syndrome numbers were significantly higher. They were in the 70s% and 80s%.
If you add that into the equation, it almost seems that that class of drug, although as effective as it is, you really need to know what you're doing when you use them. Again, therefore, the whole underlying of what type of patients do you give this product to becomes so much more important. I think for the bispecific antibodies, you have seen mosunetuzumab results so far. There are other products out there that are also under development that we don't know these results for. It is promising from an efficacy point of view, but we only have clinical data. We don't have clinical experience in the real world yet from these products, and we need to have that before we can make further estimations.
The last point I would add on bispecifics is we also don't know the price. What are they going to cost? So again, that is something that is outstanding. That's something that we just have to wait for.
Thank you. That completes all of the questions that were submitted online. Erik, I will hand back to you for any final comments. Thank you.
Thank you so much, Fraser, for helping with that. I thank you to all of you that are sticking with us and that are supporting us, both you here in the room and those online. I don't think any of us could have predicted the kind of impact we've seen both from Omicron and what we're going through with regards to geopolitical issues. We truly appreciate the partnership with you investors. You are our owners. Trust me when I say we do everything we can, 24 hours a day to do as good as we can for Betalutin and for you. Thank you for the collaboration, the conversation, and we look forward to seeing you the next time around. Thank you.