Medivir AB (publ) (MVIR) Earnings Call Transcript & Summary

Welcome to Medivir Q4 Report 2023. [Operator Instructions]. [Audio Gap]

Thank you, and welcome, everyone, to the Q4 conference call for Medivir. Let's get right into it. We'll touch on three different sort of topics today in today's call. First and foremost, we have made significant progress in quarter 4 of 2023. The Fostrox-LENVIMA study continues to progress very nicely. With regards to patients staying on treatment. We are seeing improved benefit, and we had our first external data presented at ASCO GI conference just after New Year's. As we communicated in Q3, we have been focused on accelerating the fostrox development program towards initiating a pivotal Phase IIb with the aim of gaining accelerated approval. We believe that the data and the clinical benefit we're seeing with the data is strong and the unmet medical need in the second-line HCC population is significant as there are no approved treatments beyond or after current standard of care in first line. And we have also, with regards to acceleration activities, taking strides with regards to CMC and also initiated our regulatory processes to get discussions with regulatory authorities on study design of the upcoming study as well as initiated clinical preparations, discussions with CROs. We'll talk -- we'll give an update on the fostrox LENVIMA data today. The clinical benefit we are seeing continues to go from strength to strength. We have more than 40% of patients still in the study and data continues to improve. And Pia will go through the details in a little bit. And finally, great news to see one of the out-license programs, the USP1 program, which was a preclinical program out-licensed to Tango Therapeutics. That now has a name, the molecule developed by Tango, TNG348 and they moved into the clinic with a first in human trial towards the end of December, so they moved into Phase I too. And Fredrik will give an overview of the program and what they are doing at the moment. So presenters today, apart from myself, are CMO, Pia will go through the data; Fredrik Oberg, our CSO, as mentioned, will go through the TNG348 program. And Magnus will touch on the financial highlights, of course. In terms of the highlights during the last quarter or the last sort of few months, first and foremost, the fostrox LENVIMA program keeps improving. The magnitude of clinical benefit that we're seeing in this study is sort of outperforming what can be expected of standard of care in the second-line HCC setting. We now have a time to progression that has increased to more than 6 months, which is sort of almost double what you have seen previously in second-line HCC studies. And even more encouraging is that patients are staying on treatment longer than anticipated, as mentioned, more than 40%, and that's a number that we have sort of mentioned for a while. So it's been a while since we actually have seen any patient show tumor progression and leave the study. We also did a capital raise in December and in January, and that enables us to sort of continue our acceleration activities as we move forward towards initiating a registrational Phase IIb with accelerated approval intent. Liver cancer is a challenging disease to treat. And we believe that sort of having an organ-specific targeted approach that we do have with -- sorry, with fostrox is the key to improving clinical benefit for patients. If we look at the primary liver cancer and how it is treated today; in first-line setting, today, there is a standard of care and immunotherapy combination that has shown improved benefit for patients. But even with that, there are still only 30% of patients that respond to treatment and the time to progression sort of across the first-line studies with immunotherapy combinations, is somewhere around sort of 6.5 months. So still limitations in terms of what you can expect as a patient. If you move to second line, the situation gets sort of further worse. One, there are no approved treatments today. And when we look at the treatment guidelines and we speak with sort of global experts in the field, they all say the same thing. They recommend clinical trials as the first option partly because the evidence for benefit in terms of what has been shown previously in second line is not sort of very good. In terms of those studies that has been done, we are seeing in second line somewhere along the lines of a 10% response rate and time to progression of, on average, 3.5 months. So when we look at our data, of course, that is what we need to sort of benchmark against in terms of what we need to improve on. A key strategy to improve treatment effect across cancer, sort of cancer types or for cancer patients, is to try to, of course, deliver the drug as targeted as possible to the tumor. And if we look at that today, there are two ways or two approaches that can be done. There is, on the one hand, on the left-hand side, the antigen-specific targeting or there is the organ-specific targeting. Antigen-specific is, of course, used by the antibody drug conjugates and is especially suitable for cancer types where there's a high expression of the target antigen selectively on tumor cells. That has been shown in a number of tumor types, I think that maybe breast cancer in HER2 is the most sort of famous one or the one that most people know of. However, still for an antibody drug conjugate to be effective, it does need high expression of the target antigen on tumor cells. And that is not the case across all tumor types and liver cancer is perhaps the one that stands out the most with regards to being heterogeneous cancer without specific target antigen on tumor cells. So if we want to achieve a targeted delivery of the drug to the tumor cells, then we need to find a different way. And this is where the organ-specific targeting that we're utilizing with fostrox is a different way of doing this to ensure that we can deliver the drugs as effectively as possible to where it needs to be, while minimizing damage to the healthy cells. So we do believe sort of the approach that we're taking with fostrox is the key to the improved clinical benefit that we're seeing in the ongoing Phase IIb or Phase Ib, Phase IIa study. And with regards to what we are seeing in a bit more detail, I'll hand over to Pia to go through the data.

Thank you, Jens. A very nice introduction and also to explain what actually the mechanism of action is that we are utilizing in the study. And we recently presented data from the study that Jens mentioned at ASCO GI in San Francisco. And here today, we will give a following update actually at a later time point here in February 14. So it's really, really fresh. The study, as you can see to this slide, just to remind, I'm sure you have seen this before, if you have listened to us is still ongoing, and it was a dose escalation and dose expansion phase. It was in second-line liver cancer, and it was in the Fostrox plus combination with LENVIMA. So the study was finally enrolled with the 21 patients. And what is important to know here is that we had a generous inclusion criteria, actually 19% of the patients had two prior treatments and 67% of the patients had hepatic -- extrahepatic metastasis, meaning metastasis outside the liver. And we also allowed all grade of macrovascular invasion. And why I'm saying this is that it's a very bad prognostic sign if you have a complete macrovascular invasion, but these were allowed into our study. All the patients had tumor progression on prior treatment and Tecentriq-Avastin was used in 86% of the patient. We can go to the next slide. So the current data, again, they are from February, just fresh from the press, and with seeing this progressive disease on prior treatment, it was very encouraging to see that now 24% of the patients have an objective tumor response. And you can see that in the green bars to the right on this slide. And they needed to have -- if you have an objective response rate, you need to have more than 30% reduction in the tumor size. But we could also see that 75% of the patients had an overall tumor shrinkage on fostrox-LENVIMA. So how does this sort of relate to the longer-term efficacy. And the improved response that we see in this study was reflected during follow-up. And we could see a durable clinical benefit and most importantly, an ability to stay on the treatment over time with, as Jens already said, that we have more than 40% of the patients still ongoing in the study. As I said, again, overall response rate was 24% and the disease control rate, and while we are mentioning this is that in liver cancer, also disease control is actually seen as a response. So the disease control rate includes not only partial and complete response, but also disease control rate and it was 81%. And now with the updated data, we have 6.3 months of time to progression currently. And I will just say, if you look at the swimmer plot that two patients have been ongoing in the study for more than one year, and the patient with the shortest follow-up has now been treated for 5.5 months. You can see also here a little pinkish text box at the end that, again, as Jens said, it is around 3.5 months when we look at the time to progression expected in the second line. And already now, we can see 6.3 months. So can you go to the next slide. So we have actually shown this, almost the same slide, at our webcast after ASCO. But we were really interested to understand sort of how does this time to progression of 6.3 months relate to what the patients have had on prior treatment because that is often very prognostic or predictive or what you will see in the second line treatment. It is also important to know that if the patients haven't had any successful outcome or have suboptimal response on prior treatment, would they later respond on fostrox. And what we can see here, now we have 6.3 months, yes, I already said that, is that when we looked at prior treatment to the left here, it showed that there were no real correlation and patients who had a short duration of prior treatment could actually have a longer benefit with fostrox LENVIMA. And again, interesting was to see that the median TTP here with prior treatment of 5.6 months was somewhat shorter. It is usually longer. And with this combination, we are again very encouraged about not only the response rate but also the durability of the efficacy. Can you go to the next slide. So in order to have efficacy, it was more or less a prerequisite is that the patient actually can tolerate the treatment without seeing any compromising side effects. And in this study, where we added fostrox to LENVIMA, we showed a really good safety and tolerability profile where there were no reports of any new unexpected safety events. And we have said this before, and it's still true that the side effects related to fostrox, they were mainly hematological, and they were temporary which means that 70% of the patients could continue with the full dose without having any need for discontinuation or dose modification. Importantly here is obviously that the patient continued to tolerate LENVIMA because we are adding fostrox on top of LENVIMA. And we couldn't see any increase in dose modification or discontinuation on LENVIMA either compared to what you usually see when you have LENVIMA as monotherapy. In short, sort of the combination was tolerable and -- which was also shown in the previous slide where the patient actually could stay on the treatment for a longer period of time. So can you go to the next, slide. So the current result, which was just shown showed superior efficacy compared to second-line HCC. And if we look at all the parameters you usually look at when you compare efficacy, this is, of course, an indirect comparison with standard of care in second-line HCC. We had an overall response rate of 24% where we are right now, and this should be compared with the 10% in second line HCC with current standard of care. The disease control rate of 81%. It is around 65% in standard of care. And here, we have a 6.3 months of time to progression, which would be compared to 3.5 months. We can go to next slide. This means that with this promising data, and I know that Jens already said this, but I will repeat it, we are now accelerating the next step in the development of fostrox, and we are planning a randomized Phase IIb study with registrational intent. So the eligible patients will be a little bit more narrow because they need to have received only one prior IO combination, and that is standard of care today. The randomization will be a 2:1 with fostrox plus LENVIMA versus LENVIMA alone, and the primary endpoint is progression-free survival. To pressure test the study design, we actually took the possibility since we were in San Francisco, we met with so many of the global experts to pressure test. Is this the right way to go about a study? And the feedback we received was extremely positive, I must say. We had a strong support for the study, and it is because it is an underserved population. The guideline recommend clinical trial because there are no regulatory approved treatments, and there is no consensus in how to treat this patient in the second-line setting. LENVIMA was absolutely considered as the best combination partner in second line and also very encouraging was that they expressed a keen interest in participating in the study. So what we need to do now is obviously that we need to confirm the study design in the ongoing FDA interactions as well. So with that, over to Jens.

Yes. And I'll pick up on that just in terms of what is happening at the moment, what did we do in Q4 and what are we doing going forward? And then picking up on Pia's point on FDA, we can look on the bottom. From a regulatory perspective, we did have an initial FDA Type D meeting where there were a couple of topics we needed to clarify with the FDA and got sort of positive response on. But the important kind of the bigger meeting is what we then did call an FDA Type C meeting. That is where we take our proposed study design, our proposed development program and discussed in order to confirm with the FDA that this is an appropriate way to go. That process is now ongoing, and we will, of course, sort of communicate sort of outcomes of those discussions. And in order to have U.S. hospitals be part of this study, we need to open an IND, a so-called Investigation of New Drug, and that will also then happen sort of after the FDA Type C meeting. So that's sort of well underway. What happened maybe a bit earlier, what we really needed to accelerate in Q4 2023, as you see on the slide, is to initiate some development work on CMC side from a kind of formulation of drug substance, drug product. And that we did in Q4, and that's now ongoing with regards to preparing for the Phase IIb study start. And then on the clinical side of things, as Pia mentioned, engagement with KOLs, investigators and also engagement with our advisory council in terms of understanding appropriateness of study design so forth. Again, sort of we did that in Q4 2023 and continue with that in '24. Now we're taking the next step in terms of finding the best possible CRO partner with regards to executing the study. So the development of fostrox is accelerating well -- sort of well in line with what we we're planning and what we've communicated sort of after Q3 results. So -- and maybe this is a bit early, but just for the sake of the argument, we are focusing on second line, as you see on the left, it is our kind of fast-to-market opportunity because of the significant unmet need. But as a locally or organ-specific targeted drug, there is clearly opportunity to look beyond second line and sort of we are getting sort of feedback from our experts that sort of we should be looking towards first-line setting as well and adding it on top of the combination alternatives in first line. So we are looking ahead, and we do see significant sort of future development opportunities beyond the second-line setting, but you also need to start somewhere. Second line is a significant unmet need, highly underserved population, and it is a significant value opportunity as well. So that is our sort of fast-to-market lead indications. So with that, we'll move it as there's been sort of exciting news in other parts of the pipeline with regards to the partnering programs, specifically TNG348. We will sort of touch a little bit on that. And as you see here, we do have fostrox as our in-house program that we focus our efforts to, the out-licensed programs are run by our partners without sort of further investments from our side. And the most exciting piece of news in Q4 was the [indiscernible]Tango. So just to provide a little bit of an intro to what TNG348 is and what they are doing at the moment. Fredrik?

Thank you, Jens. So as Tango is making good progress in this project, we think it would be a good idea to describe a little bit more about what USP1 inhibitor does. So USP1 or Ubiquitination-specific proteases 1 cleaves off ubiquitin molecules from target proteins. And one key target protein is PCNA, which is a protein involved both in DNA replication but also in DNA repair. So it needs to be mono-ubiquitinated to start with. And then this molecule needs to be cleaved off in order to -- for the DNA repair process to proceed. So what TNG348 does, it inhibits the USP1 protease activity, so it doesn't cleave off ubiquitin. It means that PCNA will accumulate several poly-ubiquitinated molecules. And this will lead to cessation of the DNA repair and degradation of PCNA. And as you may know, cancer cells are often reliant on a few DNA repair mechanism because they usually have mutations in several repair mechanisms. And such a mechanism is mutations in BRCA1 or 2, BRCA1 or 2. And these mutant cells are essentially very sensitive. They rely on this PCNA-driven translesion synthesis. So they are very sensitive to inhibition of USP1. So there's a good scientific rationale, but also as we see in the next slide, solid preclinical data demonstrating that mutant or cancers with mutant BCRA1 or 2, for that matter, genes are sensitive to inhibition with TNG348. So these are our graphs showing tumor growth, patient-derived xenograft. So tumor cells from patients with breast cancer or pancreatic cancer, transplanted to mice, and these mice are then treated with the drugs indicated here. So it's shown that also as a single agent, TNG348 does inhibit mutant cancer cells or the tumor growth in these mice. But also you can enhance that activity by inhibiting another important enzyme in DNA repair, namely the PARP enzyme, by PARP inhibitors. So there is a good rationale both for single agent and combination studies with TNG348 together with PARP inhibitors. So if we move to the next slide, as Tango announced early January, they had dosed their first patient in the clinical study with TNG348. So they are in the dose escalation phase right now where they are trying -- testing 2 arms, TNG348 as a single agent or in combination with olaparib, which is a PARP inhibitor. And their clinical development plan is then to move into specifically then BRCA-mutated breast or ovarian cancer with single agent and also the combination in these two indications increase -- including also pancreas and prostate cancer. And as you see on the right-hand side, this is because the mutational frequency of BRCA genes or other genes involved in homologous recombination are relatively high in ovarian, breast, prostate and pancreatic cancers. So we are really happy that they are moving this rapidly forward. And this is really what you want to see when you out-license a program, a very good progress in the clinical development.

And Tango have moved the program along with sort of very nice speeds and communicating sort of strong enthusiasm for this. PARP inhibitors have now been sort of well-established standard of care in BRCA mutant cancers sort of as blockbuster options. So adding benefit on top of a PARP inhibitor would have a significant value upside for USP1 inhibitor. So we look forward to reporting sort of future progress of TNT348. With that, financial, Magnus?

28:05 Thanks, Jens. Please, you can move to the next slide, please. we can see the financial summary for the quarter 4 and for the financial year 2023 and all numbers are in million SEK. From a financial viewpoint, Quarter 4 was according to our plan from a cost perspective. Turnover for quarter 4 amounts to SEK 4.4 million, which relates to the royalty income was [indiscernible] and also the milestone income related to Tango. That dose the first patient, as we have mentioned right now. Year-to-date, turnover is higher and it almost relates to the milestone income. Other external expenses are higher compared to last year in the quarter and relates to the cost for the ongoing combination study. Year-to-date is in line with last year. Personnel costs are higher and relates [ performance ] to more employees compared to last year and [indiscernible] accruals. The operating loss for quarter 4 was SEK 21 million, which is in line with our estimations for the year. The cash position at the end of the year is SEK 169 million, and we received the right issue proceeds in December, but we have paid most of the transaction costs related, we paid up in January this year. And also, as Jens has mentioned, we carried out a directed issue to Hallberg management, which we received in January this year. And according to our current plan and assumptions, the cash run rate will be into Q1 2025. And with this, I will hand back to you.

So before Q&A, just sort of a summary of things before we open up the call. So we continue to strongly believe that the combination of fostrox together with LENVIMA has the potential to transform second-line primary liver cancer or HCC. We are seeing sort of the smart organ-specific approach with fostrox that selectively kills liver cancer cells while sparing healthy C cells is showing encouraging clinical benefit. The data keeps getting stronger and stronger as patients stay on treatment longer than expected, sort of further improving or outperforming sort of what can be expected of standard of care in the second-line setting. The fast-to-market opportunity in second line is sort of as PR, so communicated previously, it is highly underserved. And it is a high-value population where there is significant value upside also beyond that indication as we move forward. So with that, we stop there and we move to Q&A.

[Operator Instructions]. The next question comes from Richard Ramanius from Redeye. Please go ahead.

Hello, I have a couple of questions in different. Let's start with the -- or is the numbers you presented confirmed objective response rates.

The objective response rate, ORR, I should have added that in most of the cases, it's actually confirmed. And to be honest, I haven't looked at the data where it is not confirmed. So I will have to come back to you for that. It was not the primary endpoint, and that is the reason that we have added objective response rate and not overall response rate.

Okay. But this overall impression is quite good. Could you say anything about median overall survival? Do you have any projections for that? Or when could you report?

So the median overall survival. In this study, the patients were treated until they progressed. And after that, we had a follow-up for 6 months for overall survival. So as you can understand, if the patients did not die during the 6 months, we will not have the opportunity to report that overall survival. So -- and that is the reason why we need to move forward into a new trial where we have a randomization. It's not only for the LENVIMA comparison, it's also to have really conclusive data, but we will have time to progression on progression sort of progression-free survival. We are reporting time to progression due to the fact that in progression-free survival, you also count in the overall survival. And yes, one more thing I need to say here. And that is that in the studies, I mean, there are not many studies for LENVIMA, monotherapy. But in the studies where we have looked, the progression-free survival and time to progression has been very similar due to the fact that they progressed this early. So that's why these two parameters or endpoints are relatively comparable in HCC.

Yes. Right. And I was thinking about the responses you were talking about at the GI ASCO conference you were at and the strong support. And it's interesting that clinical trial is recommended for Phase II patients. Shouldn't that play to your advantage would -- I mean, that would suggest you could recruit patients really fast in a Phase II trial? And also like to ask what do you think about academic support. I guess you're not interested in getting such a trial sponsored even if you could. But what kind of academic support could you get for such a trial?

Yes. If I start with the recruitment, you are absolutely correct. So we could see that already in the trial that is ongoing now, the Phase Ib and IIa. It was a fast recruitment. It was a huge interest because they cannot access LENVIMA. LENVIMA is improved in the first-line setting, and it's not regulatory approved in the second-line setting, which means that we hope still since there is nothing of regulatory approval segment setting to be able to recruit really, really quickly in the study. And that is the reason why we are ramping up all the preparation activities to be able to open this study as soon as possible. That was the first one. The academic support. Sort of we have the academic support, and we realize that very, very strongly since we talked with a global expert from the U.S., from Asia and from Europe. When it comes to consortium, if that is what you are talking about, obviously, we are going to look into that more in detail when we do our feasibility to see if there is, for example, any research consortium, particularly in the U.S. that might be interesting to participate, but we need to have it as a company-sponsored trial. We cannot have it as an academic trial because then it will be very difficult to have the correct monitoring and everything that is required for regulatory approval.

Yes. Okay. I had a question about business development for Jens. Since you have although simply small, but results convincing, you also have right regulatory pathway and you have the right market, could you discuss which of these points you think is most important because we've seen in the last year that large pharmaceutical companies say they're not -- they don't seem to be that interested in early-stage assets, but this is a pivotal trial that makes it late-stage assets. How does that affect interest?

Yes. And I think that's -- it is a fair statement. Larger pharmaceutical companies, they can afford to sort of wait somewhat, I sort of move sort of wait for late stage. We are now moving to late stage. So one of the key elements as sort of Pia commented on previous is the regulatory path. And that is why we have sort of emphasized our focus and prioritized sort of moving to regulatory interactions, specifically focused on FDA with regards to generating clarity on study design and primary endpoint size of patient population, et cetera, because we do anticipate that is going to be a critical element of any partnering discussions. And we focused on the U.S. because we know that sort of a majority of other regulatory agencies will look to the FDA, and they will sort of follow how FDA guides. So always difficult to sort of make an assessment of which -- what parameters are most important. I think it's important to sort of kind of -- it's important to conclude that the clinical benefit we are seeing is going to be sort of the first thing you look at. If there isn't a convincing clinical benefit, if we're not seen as we're adding anything on top of current standard of care, clearly, that will deter sort of people from being interested. But as we move towards pivotal stage, yes, sort of as much clarity as possible on regulatory path and feedback from regulatory authorities will also be important. And as mentioned earlier, that process is ongoing and is well underway, and it was encouraging, quite encouraging that the feedback from the leading global experts we met at ASCO GI was quite -- I'm looking for the right word, [indiscernible] [ some stemming ]. It was quite conclusive and they all communicated the same message i.e., in terms of supporting the approach we're taking with the proposed IIb study.

Okay. So some final financial questions, if you bear with me for Magnus. First of all, about working capital, you had a quite -- you see a positive effect on cash flow in this quarter that has burned quite a little, but you have a negative working capital, would that affect -will that reverse. That should reverse in the coming quarters, right?

Yes. Thank you, good question. Yes, that's the first statement. As I said, all the transaction costs that's related to the right issue, they were paid in January and then there were some accruals at the year-end that will be paid in quarter 1 as well. So you are correct, Richard.

Final question, I wanted to ask about the milestone structure for the Tango agreement. Since you got paid roughly around SEK 4 million for start of Phase I, would it be correct to assume then that it is very back heavy.

I mean we have not disclosed the terms of the agreement. But like I say, the figure that you mentioned for the milestone payment that's kind of accurate that you say. We have not disclosed that, but that's what you will be shown in the annual report and will be shown later on. So it's around that figure, I would say.

And yes, it is relatively -- so we are not going into details because we haven't disclosed but it is a relatively back heavy sort of standard sort of licensing agreement, especially sort of considering that it was out-licensed as a preclinical program.

The next question comes from Joe Pantginis from H.C. Wainwright.

Two questions, please. First, maybe for the responders in the study, can you disclose any color about whether any of those were the dose reduction patients? And second question is going into the Type C meeting. Can you disclose sort of what your rate-limiting steps or ongoing discussion points are with regard to the final study design.

Thank you for the question. And yes, there were some of those patients who actually are responding who dose reduced. Just talk about sort of what fostrox is. Fostrox is this targeted drug to the liver where it is released. So it's really dependent on the liver function, the enzymes in the liver and the liver functions of the patient. Which means that it's difficult to understand sort of the tolerance for one specific patient. So that's why it's important that we have a dose that is on as high level as possible. And we sort of -- you need to expect some of the dose reduction. So yes, it was. That was a long answer. Sorry, I forgot the next question. The regulatory, yes. So what we are waiting for is really to have the interaction with FDA to finalize the study design. We have done what we can do until now with trying to sort of structure primary endpoint and all the substance but of course, if there is something that they had opinions or we need to be design part of it. But I would -- now I'm really cockish, but this study design has resonated very well with the majority of all the experts that we have been talking to. So let's hope for the best.

And I think that the added color, Joe, I mean so some of the -- I mean the assumption of clinical benefit that we are making sort of the 6 months PFS versus 4 months and whether that's clinically relevant, et cetera. Those are some of the design points that sort of we have seen as key with regards to, and we think that the FDA will view as key as well. And that's where, as Pia concluded, we've been encouraged by the feedback from the experts agreeing with sort of the assumptions that we've made.

The next question comes from Klas Palin from Carnegie.

And just quick question about -- to clarify this Type C meeting, do you expect this to be finalized in the first half of 2024?

That's correct.

Perfect. And also about your IND that you are intending to open up in the U.S. Do you expect you need to do some sort of a bridging study before being able to recruit patients -- American patients into the pivotal study?

So no, we don't need to have a bridging study, but we need to have the IND included. That is what we need. So there is no need to have any additional U.S. patients before you go and open the IND. And the IND will be opened on the randomized Phase II study. That's why we need to sort of have the FDA feedback first.

The next question comes from Jason McCarthy from Maxim Group.

Can you just go back to the Phase I/II study and walk us through what the median follow-up time has been? I know that TTP 6.3 months. And with that, how far out are you going to continue to monitor these patients?

That's a very good question, and we are actually planning to start closing the study this year. And the reason for that is that it is a heavy work for the institutions and also for the patients to be controlled this regularly because we have CT scans and MRI every 6 weeks, you can only imagine. So that is one thing. And the other thing is that even if we have 40% of the patients still in the study, we see the safety data as long in HCC second-line population and also the efficacy data that we can get from this study is starting to be really, really mature. So our focus needs to be to start the randomized Phase IIb study now, and that's why we are planning to close out this study this year.

Got it. And I know it's a little bit down the road. But considering first-line HCC therapy, what's the expectation of improving or potentially improving response rates in first line if Tecentriq or checkpoints with the TKI or they're already being used, right? Or would you have to use kind of that combination for a comparator arm versus your own combination with TKI?

So we are talking about the first line here, and it's very interesting, and I'm sure that you are aware that there are quite a lot ongoing where you add something on top of Tecentriq-Avastin. But since we also need to have more data with this combination. So we haven't decided since we are focusing on the second line now. But that needs to be established first the tolerability.

But I think I'll say the following. The feedback from the advisory council when we discuss with them, okay, what sort of path do we have forward, they are relatively sort of clear in their advice to us that yes, let's move with speed in second line because the unmet need is clearly there and sort of we're lacking options. But we also get the same strong message that you should start exploring first-line as soon as possible because there is -- as we sort of concluded to earlier that there's still only 30% response rate and the PFS is relatively short in second line, in first line as well. And the guidance is to we should explore adding fostrox on top of sort of either Tecentriq-Avastin or another immune therapy combination. So they see a triple combination as the logical sort of next step rather than necessarily sort of compete taking fostrox LENVIMA and competing with Tecentriq-Avastin. So triple combination is kind of where they would be steering us to go as a first line option.

I will only add to that. The reason why they do that is also that it is a completely different mechanism of action, and it has been very tolerable. So -- and if you have three different drugs in a very frail patient population, the tolerability is going to be key. So we will -- I think we will have to come back on more details on that.

Or can I elaborate even further? No, no. I mean we also do see that the landscape will probably shift a bit with regards to the data we're seeing,, Tecentriq-Avastin has shown in the adjuvant setting. And we've seen with the EMERALD study in terms of sort of treatment sort of immune therapy combinations being used earlier. So it is not unlikely that as they are used in earlier settings when patients progress and you come into today's first-line advanced setting, then a combination like fostrox LENVIMA, which will be tested in second-line and hopefully approved might actually be moved up to first line just because the immunotherapy combinations are being used in earlier setting. But again, that's something that the future will need to hold. At this stage, we focus on showing the benefit of fostrox plus LENVIMA in order to get to market as quickly as possible because that's going to provide the greatest benefit for HCC patients.

Got it. Last question, just briefly, what is the current cost per patient in the ongoing trial? Do you expect similar cost per patient for a U.S.-based study where you're going to have about 210 patients for the Phase IIb?

Can I respond?

You can respond. I think it's going to be difficult ...

I mean the cost of patient. It's an estimation, and is so dependent on where you are, right? Now we have been in Spain, South Korea and in the U.K. It's completely different if you go to the U.S., for example. So the cost is going to increase for these sites obviously. But -- so that's why it's going to be difficult. But somewhere between SEK 1 million and SEK 2 million per patient maybe?

In SEK.

In SEK, sorry.

I was scared as you were talking.

And I mean, it's difficult to compare with the current study because current study, as Pia has alluded to, they are required to do CT scans. They are required to do MRI scan. So again, cost for the study is going to also be dependent on examinations done and what are we asking them to do? What will the FDA require us to do, et cetera. But yes.

There are no more questions at this time. So I hand the conference back to the speakers for any closing comments.

Thank you all for dialing in. Sort of -- I'll just sort of go back to this one. Again, as we have hopefully conveyed, we are quite excited by what we are seeing in the ongoing study. Patients are staying longer on treatment. Guess that, on the one hand, generates additional costs for a study, but most importantly, it generates additional benefit for patients, and it makes us even more confident in moving the program ahead with as much speed as we possibly can. We truly believe that there is an opportunity to get first to market and change how second-line HCC patients are being treated. It is highly underserved. It is a high-value population. So with that, thank you for dialing in and look forward to sharing additional updates as we move forward.