Welcome to Medivir Q4 Report 2023. For the first part of the conference call, the participants will be in listen-only mode. During the questions and answer session, participants are able to ask questions by dialing hash five on their telephone keypad. Now, I will hand the conference over to CEO Jens Lindberg. Please go ahead.
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 four 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 II-B, 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. We have also, with regards to acceleration activities, taken 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 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.
Finally, great news to see one of the outlicensed programs, the USP1 program, which was a preclinical program outlicensed to Tango Therapeutics, that now has a name, the molecule developed by Tango, TNG348, and they moved into the clinic with the first-in-human trial at towards the end of December, so they moved into phase I/II, and Fredrik will give an overview of the program and what they are doing at the moment. So, presenters today, apart from myself, our CMO, Pia, will go through the data. Fredrik Öberg, our CSO, as mentioned, will go through the TNG348 program, and Magnus will touch on the financial highlights, of course. In terms of sort of 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 six months, which is sort of almost double what you have seen previously in second-line HCC studies. 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 II-B 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 sort of primary liver cancer and how it is treated today, in first-line setting, today, there is a standard of care, an immune therapy 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 six and a half 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 a time to progression of, on average, three and a half 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 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, and I think that maybe breast cancer in HER2 is the most sort of famous one or the one that most people know of. However, sort of it's still sort of for an antibody drug conjugate to be effective, sort of 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 a 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. 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 II-B or phase I-B, phase II-A 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. Very nice introduction and also to explain what actually the mechanism of action is that we are utilizing in this study. We recently presented data from the study that Jens mentioned at ASCO GI in San Francisco. Here today, we will give a following update actually at a later time point or here in February fourteenth. So it's really, really fresh. The study, as you can see on this slide, just a reminder, 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.
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 extrahepatic metastasis, meaning metastasis outside the liver. We also allowed all grade of macrovascular invasion. 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 patients. We can go to the next slide. 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.
You can see that in the green bars to the right on this slide. 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 and LENVIMA. We can go to the next slide. So how does this sort of relate to the longer term efficacy? 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 said, again, overall response rate was 24%, and the disease control rate, and why we are mentioning this is that in liver cancer, also disease control is actually seen as a response. So the disease control rates 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 this swimmers 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 we can go to the next slide. So, we have actually shown this almost the same slide at our webcast from 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 prognostics or predictive of what we 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, 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 that had a short duration of prior treatment could actually have a longer benefit with Fostrox than 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 a 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 we 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, a disease control rate of 81%. It is around 65% in the standard of care, and here we have 6.3 months of time to progression, which should be compared to 3.5 months. This. We can go to the 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 II-B study with a registrational intent.
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 two to one with Fostrox plus LENVIMA versus LENVIMA alone, and the primary endpoint is progression-free survival. To pressure test this study design, we actually took the possibility, since we were in San Francisco, and we met with so many of the global experts to pressure test is this the right way to go about a study? 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 treatment, 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.
Yeah, 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 sort of 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 discuss in order to confirm with the FDA that this is an appropriate way to go.
That process is now ongoing, and we would, of course, sort of communicate sort of outcomes of those discussions. In order to have U.S. hospitals be part of the study, we need to open an IND, a so-called Investigational 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 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 II-B study start.
Then on the clinical side of things, as Pia mentioned, engagement with KOL 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 2024. 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 were planning, and what we communicated sort of at the 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's a significant value opportunity as well. So that is our sort of fast to market lead indication.
So with that, we'll move in as there's been sort of exciting news in other parts of the pipeline with regards to the partnering program, specifically TNG348. We will sort of touch a little bit on that. As you see here, we do have Fostrox as our in-house program that we focus our efforts to. The outlicense programs are run by our partners without sort of further investments from our side. The most exciting piece of news in Q4 was the one communicated by 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 a USP1 inhibitor does. So USP1, or ubiquitin-specific protease 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 monoubiquitinated to start with, and then this molecule needs to be cleaved off in order for the DNA repair process to proceed. So what TNG348 does is inhibit the USP1 protease activity, so it doesn't cleave off ubiquitin.
This means that PCNA will accumulate several polyubiquitinated 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 mechanisms because they usually have mutations in several repair mechanisms, and such a mechanism is mutations in BRCA1 or BRCA2. 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 BRCA1 or BRCA2, for that matter, genes, are sensitive to inhibition with TNG348. So these are graphs showing tumor growth, patient-derived xenografts, 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's 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 testing two 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, increasingly including also pancreas and prostate cancer.
And as you see on the right-hand side, this is because the mutation or 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 their clinical development.
Tango have moved the program along with sort of very nice speed and communicating sort of strong enthusiasm for this. PARP inhibitors have now been sort of well established as standard of care in BRCA mutant cancers, sort of as blockbuster options. So adding benefit on top of the PARP inhibitor would have a significant value upside for a USP1 inhibitor. So we look forward to reporting pro sort of future progress of TNG348.
With that, financial, Magnus?
Thank you, Jens. Please, you can move the next slide, please. We can see the financial summary for quarter four, for the financial year 2023, and all numbers are in million SEK. From a financial viewpoint, quarter four was according to our plan from a cost perspective. Turnover quarter four amounts to SEK 4.4 million, which relates to the royalty income for XALKORI, and also the milestone income related to Tango. Those are the first patients, as we have mentioned right now. Year to date, turnover is higher, and it almost relates to the milestone income. Other external expenses are high compared to last year in the quarter, and it relates to the cost for the ongoing combination study. Year to date, it's in line with last year.
Personnel costs are higher and relate foremost to more employees compared to last year and year-end accruals. The operating loss for quarter four 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 rights issue proceeds in December, but we have paid most of the transaction costs related. We paid that in January this year. And also, as Jens has mentioned, we carried out the 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 that sort of the smart organ-specific approach with Fostrox that selectively kills liver cancer cells while sparing healthy 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 this second-line setting.
The fast to market opportunity in second line is sort of as PI sort of 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.
If you wish to ask a question, please dial pound key five on your telephone keypad to enter the queue. If you wish to withdraw your question, please dial pound key six on your telephone keypad. The next question comes from Richard Ramanius from Redeye. Please go ahead.
Hello. Good, good. Good afternoon. I have a couple of questions in different areas. Let's start with the ORR. Is the numbers you presented confirmed objective response rates?
The objective response rate, ORR?
Yeah.
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 always. We have all, we have added objective response rate and not overall response rate.
Okay, but the 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 six months for overall survival. So as you can understand, if the patients did not die in during this six months, we will not have the opportunity to report that overall survival. 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.
Okay.
And yeah, one more thing I need to say here, and that is that in the studies, I mean, there are not many studies with 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 progress this early. So that's why these two parameters or endpoints are relatively comparable in HCC.
Yeah. 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 a clinical trial is recommended for phase II patients. Shouldn't that play to your advantage? I mean, that would suggest you could recruit patients really fast in a phase II trial. I'd 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?
So if I.
Just to be with it.
Yeah, if I start with the recruitment, you are absolutely correct. So we could see that already in the trial that's ongoing now, the phase I-B and II-A. 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, regulatory approved in the second line setting, to be able to recruit really, really quickly in this 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 realized that very, very strongly since we talked with global experts 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.
Yeah. Okay, thanks. I had a question about business development for Jens.
Yep.
Since you have, although sample is small, but results convincing. You also have the 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, they don't seem to be that interested in early-stage assets, but if this is a pivotal trial, then that makes it late-stage asset. How does that affect interest?
Yeah, and I think that's a. It is a fair statement. Larger pharmaceutical companies, they can afford to sort of wait somewhat, i.e., sort of move, sort of wait for late stage. We are now moving to late stage, so I guess one of the key elements, as Pia commented on previously, is the regulatory path. And that is why we have emphasized our focus and prioritized 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 on 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, something. 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 to-be study.
Okay, thanks. Some final financial questions, if you bear with me.
Sure.
So, for Magnus, first of all, about working capital, you had a quite, as you say, positive effect on cash flow in this quarter. That is, you burned quite little, but you have a negative working capital. Now, would that reverse in the coming quarters, right?
Yes, thank you for the question. Yes, that's a fair statement. As I said, all the transaction costs that related to the rights issue, they were paid in January, and then there were some accruals at the year-end that will be paid in quarter one as well. So, you are correct, Richard.
So 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 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 said, the figure that you mentioned for the milestone payment, that's kind of accurate, that you say. We have not disclosed that, but that will be shown in the annual report, as we show later on. So, it's around that figure, I would say, Richard.
Yes, it sort of, it is a relatively. Without 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 outlicensed as a preclinical program.
Okay, great. Thanks. That you've answered all my questions.
Thank you.
The next question comes from Joe Pantginis, from H.C. Wainwright. Please go ahead.
Taking the question. Two questions, please. First, maybe, Pia, 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? Thanks a lot.
Thank you for the question. 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 that we sort of you need to expect some of the dose reduction. So yes, it was. That was a long answer. Sorry, now I forgot the next question.
The regulatory, yes. So what we are waiting for is really to have the, the interaction with the 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 stats and so on. But of course, if there is something that they have opinions of w e need to redesign part of it. But I would. Now, I'm really saying that.
This study design has resonated very well with the majority of all the experts that we have been talking to. Let's hope for the best.
I think that the added color, Joe, I mean, sort of some of the I mean, the assumption of clinical benefit that we are making, sort of the six months PFS versus four 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, 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.
Okay, thank you.
The next question comes from Klas Palin from Carnegie. Please go ahead.
Yes, hi there, and thanks for taking my questions. And just a question about to clarify this Type C meeting, do you expect this to be finalized in the first half of 2024?
Yes, 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, we don't need to have a bridging study, but we need to have the IND.
Yeah.
I n place. That is what we need. So, there's 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.
Okay, great. Thank you.
Thank you.
The next question comes from Jason McCarthy from Maxim Group. Please go ahead.
Hi, team. Thanks for taking the questions. 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 the TTP 6.3 months, and with that, how far out are you going to continue to monitor these patients?
So, 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 heavy work for the institutions and also for the patients to be controlled this regularly, because we have CT scans and MRI every six weeks. So 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 need to be to start this randomized phase II-B study now, and that's why we are planning to close out the study this year.
Got it. 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 a TKI are already being used, right? Or would you have to use kind of that combination for a comparator arm versus your own combination with a TKI?
So we are talking about the first line here, and it's very interesting, and I'm sure that you're 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 need to be established first, the tolerability.
But I think, I'll say the following: the feedback from the advisory council when we discussed 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 is- there's still only 30% response rate, and the PFS is relatively short in second line, and in first line as well. And the guidance is to, we should explore adding Fostrox on top of a 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 competing, 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. I think we will have to come back on more details on that.
Or can I elaborate even further?
Oh!
No, no, I mean, we also do see that sort of 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 then, and hopefully approved, might actually be moved up to first line just because the immune therapy 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 costs per patient for a U.S.-based study, where you're going to have about 210 patients for the phase II-B?
Can I respond?
You can respond. I think it's going to be difficult to respond.
So now, I mean, the cost per patient, I know. It's an estimation, and it 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. SEK 100,000-SEK 200,000.
Thank you. Yeah, that scared us for a second.
And it, 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 scans. So again, a 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, yeah.
Got it. Thank you, all.
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 but by what we are seeing in the ongoing study. Patients are staying longer on treatment. Yes, that on the one hand generates additional costs, so 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.