Welcome to Medivir Q4 Report 2024. For the first part of the conference call, the participants will be in listen-only mode. During the Q&A session, participants are able to ask questions by dialing pound key five on their telephone keypad. Now, I will hand the conference over to CEO Jens Lindberg. Please go ahead.
Thank you, and good afternoon, and welcome everyone to the Medivir Q4 report, where we will sort of go through the progress made in the last quarter of 2024, and then looking ahead to what is about to happen in 2025. Q4 last year continued to be a good quarter with regards to momentum in our primary program, fostrox, which is our oral liver-targeted treatment in development for advanced liver cancer. We closed our phase I-B, phase II-A study of fostrox in combination with Lenvima, and we are very much looking forward to presenting the final data at the EASL Liver Cancer Summit, and that is actually taking place this week on Thursday. We closed the study while still having three patients on drug, and patients have been staying on drug and in the study longer than we—or quite much longer than we anticipated.
We closed the study in November with three patients transitioning to compassionate use. I will provide an update on those patients as well when we get to EASL on Thursday. Importantly, as we look ahead to the planned phase II-B study, which now has a name, which is the FOcuS-2 study, we got IND approval of that study by the FDA in Q4. They have approved the study design, and that is a very important milestone because that allows us to switch over our kind of preparations in other countries as well, because we want to make sure that the FDA approves of the study design. Thirdly, as we have communicated previously, we have agreed on clinical collaboration and supply with Eisai, and that collaboration is ramping up, and we have established a joint development committee.
Moving forward with that, and also then progressing plans quite quickly outside of the U.S., looking ahead to into then 2025. Good momentum. With me in the room is our CMO, Pia Baumann, and she will be going through a couple of different things linked to the IND, and also we've seen some external data sort of comparing that we can look to compare with what we have shown in our study and what we will plan to show on Thursday as well. Joined by Magnus Christensen, our CFO, who will cover sort of the financials at the end, and our CSO, Fredrik Öberg, is in the room as well for any questions as we get to the Q&A session.
Moving into looking at sort of fostrox program, as mentioned, we continue our phase II-B study initiation sort of progress, and we've also in Q4 sort of seen data presented at ESMO Asia that confirms the fostrox-Lenvima combination clinical benefit that we've seen previously. I'll hand it over to Pia to walk through the two different topics.
Super. Thank you very much. I'll continue a little bit on where we are right now and what is happening post-IND approval. The IND approval was given for, and I will continue to call this study now, the study that we are planning, the phase II-B for the FOcuS-2 study. The IND approval was received in December, and that study has a study design using a dose running, you will see it a little bit later, and that is really to select the optimized dose of fostrox and to align with the FDA Project Optimus. We have also selected a primary endpoint of overall response rate, which is also an accepted endpoint for accelerated approvals in HCCs as seen before. This study is really powered to show a clinically meaningful difference between fostrox + Lenvima versus Lenvima monotherapy.
This is sort of the base for where we are right now. We can go to the next slide. A little bit more in detail then. As I said, fostrox or FOcuS-2 study is really designed to optimize also the potential opportunity for having a breakthrough designation. Obviously, this depends on our study results, but we also aim for an accelerated approval if these study results show a little bit similar to what we have seen in the phase I-B/II-A study. In this study, which is randomized, it's double-blind. The patient that can be enrolled should have received the first line immunotherapy combination for advanced liver cancer.
In the first part, as you can see here, part one, the patients will be randomized to three arms, one with fostrox 10 mg + Lenvima, the other one with fostrox 30 mg + Lenvima, and one arm with only Lenvima. This first part, the enrollment period for enrolling these 60 patients, is assumed to be 12 months. When all the patients in part one have been followed for 12 weeks, there will be a planned interim analysis for this dose optimization with a dose selection. This dose selection is made by an independent board that is not associated with us or with the study. That is to ensure the study integrity for the full study. This is called the DSMB. It's a little bit small, but I hope you can see it.
The arm that will be selected will continue to enroll patients in part two with a one-to-one randomization with the arm that has Lenvima alone. In this process, the DSMB-selected arm will be dropped. The enrollment in part two is also estimated to take 12 months. We hope to have all the 40 sites in eight countries opening and participating. In total, we are aiming for 154 patients, and when we are at the final analysis, the assumption is a statistical power. We have calculated a statistical power for more than 80% to detect this clinically meaningful difference in response rates that we aim for. We can go to the next slide.
I already said eight countries and 40 sites, and these eight countries and 40 sites are divided globally, and the countries are in the region of Europe, Asia, and also in the U.S. to really ensure that we have a maximal speed of the enrollment, but also that we see sort of the clinical relevance in the context of regional differences. Can we go to the next slide? With the IND approval, the FOcuS-2 activities that are really crucial for study opening are progressing very nicely with the key start activities that you see on this slide, which includes site selection finalization, obviously, and initiation of the contract for the sites, the different regulatory and ethic committee submissions in the countries. We have also important the study setup collaboration with the site, which includes the Lenvima supply.
We need to have all the supply of the study drugs ready at the sites, which includes fostrox and also placebo, and all the different systems set up for data capture, etc. This is really what we are doing currently right now, and it's progressing nicely. We can go to the next slide. In all this, there's a lot of assumptions, right? To further support our assumptions, we are monitoring everything that is going on. As we talked about before, there's high unmet need in this patient population, so there is not really much going on in the second line. Our assumptions are sort of built on what we can see with Lenvima alone. The first prospective actually study that has been presented was presented at ESMO Asia in 2024. We looked at this study.
It was from Korea, 13 sites. It was a multicenter study that enrolled 50 patients. They received Lenvima after TECENTRIQ, Avastin. It was very much a similar patient population that we had in our phase I-B, II-A study with fostrox + Lenvima. In order to understand if we could confirm our assumption and what we have seen pretty much in all second-line studies, we looked at the study data. We can go to the next slide. Oh, you have already gone to the next slide. Super. This is just sort of a little bit so you yourself could see that we have similar patient characteristics when we look at age, gender, liver cancer stage, liver functions, prior treatment between those two. Again, prospective studies with Lenvima monotherapy post-IO is scary. This is the first one that we have seen. We can go to the next slide.
The outcome data from this study, from this Lenvima monotherapy study, really confirmed what has been shown previously. I am not sure if you remember what we have shown when we do this summary, and I think that you will come back to that, Jens, is that the median progression-free survival is around four months. In this study, it was a median progression-free survival of 5.4 months with a median overall survival of 8.6 months. It pretty much is similar to what we have seen before and was really confirmatory. We can go to the next slide.
If we do this nice indirect comparison, which we always do between Lenvima monotherapy and the phase I-B/II-A study with fostrox + Lenvima, there was a substantially longer time to progression, as you can see here, between what you see with fostrox Lenvima with a median time to progression of 10.9 months and compared with what we already looked at, this 5.4 months with Lenvima monotherapy. One thing that is important here, when you look at this different Kaplan-Meier curve, it is how often did you do your assessment with imaging? This might seem like a little detail, but it is really important when it comes to understanding the progression, because the more often you do an assessment, the earlier you will identify a progress.
In the study that we are comparing with, it was with eight weeks interval, and in the phase I-B/II-A study with fostrox + Lenvima, we actually did both CT scans and MRI every six weeks. We feel pretty confident with this data. We can go to the next slide. Jens already talked about this, so we are super excited to present data at EASL Liver Cancer Summit, and it is on Thursday. If you can read this tiny little fonts here, this is the title of the study. We are looking at final efficacy data, including overall survival. We are also doing a correlation between clinical efficacy and biomarkers, and importantly, we will have a final update on safety and tolerability. Stay tuned, and I hope that you will sort of see some of this data. Otherwise, you can look at our website later.
I will give it back to Jens.
Thank you. We can sort of compare the overall survival we showed then on Thursday with what we saw from the prospective Lenvima data from ESMO Asia. As Pia alluded to, one thing that we look at continuously is we try to find what is happening in the market, because as we have communicated quite regularly, and it feels maybe sometimes quite repetitive, we say that we are at the forefront of development in second line. There are very few drugs in development for second-line liver cancer. As we explore the treatment algorithm in advanced liver cancer, we can see that it is established in first-line treatment that immunotherapy combination is used, primarily TECENTRIQ, Avastin.
There are quite a few other PD-1 combinations in development in first line, and they are all sort of trying to sort of show who is the best or most efficacious treatment. Quite a few studies are ongoing in first line. If you look on the left side, if you move down to second-line treatment, there are, as we've concluded before, no approvals after immunotherapy combination in first line. There is a lack of scientific evidence as to what actually works in second line. The global treatment guidelines that exist today, their preferred recommendation is clinical trials. If there isn't a clinical trial, the preferred option by physicians is monotherapy with Lenvima, which is one of the reasons why we've combined with Lenvima. In many countries, it is not allowed and it is not funded, so it poses a challenge for physicians.
We've recently had the big GI, Gastrointestinal Cancer Congress in the U.S., in San Francisco, ASCO GI in January. There is the EASL Liver Cancer Summit taking place this week in Paris. We can summarize those congresses by concluding, again, there is very little development in second line. We've been sort of strengthened in our conviction that we are, with the fostrox Lenvima combination, at the forefront of development, and there is a very clear opportunity to move with speed and be the first approved treatment option, which is, again, why we're trying to progress the preparatory activities for the FOcuS-2 study as quickly as we possibly can. There is a very significant unmet need.
The market is a big market, and the market will probably grow even faster than many have anticipated, because one of the things we see, there is an obesity epidemic ongoing in the world with or without GLP-1s. What we see with patients that are obese, more than, for example, take the U.S. example, 45% of adults obese, more than 25% have fatty liver disease. Among other things, a study at Karolinska has shown that if you have fatty liver disease, the risk of getting liver cancer is 17-fold. It is a dramatically increased risk when patients have a fatty liver disease. The number of patients who will be incurring fatty liver disease in the coming decade is anticipated to grow quite rapidly. Significant unmet need and a large commercial potential.
If we then summarize things in terms of what we have developed, what we have shown, we have the first oral liver-targeted treatment in development for liver cancer. We have a unique mechanism of action that complements other drugs on the market. We have very nicely shown an ability to get the drug to the liver, and in the liver, we kill cancer cells and we spare healthy cells, which is extra important for patients with liver cancer. As Pia shown, the data we've shown is very competitive and shows a very strong clinical benefit compared to what can be expected with today's available treatments. There is an opportunity, if we go down to the left bottom left, there is an opportunity to move with speed to be the first approved treatment option in second-line advanced liver cancer.
Conservatively, going down to the bottom right, that market, when we get to 2030, will be valued at least $2.5 billion annually. That's likely a conservative estimate. That could be as much as sort of $3 billion-$4 billion, depending on sort of the amount of patients with fatty liver disease that then grows and develops liver cancer. A significant commercial potential. With that, I think we stop in terms of progress on the fostrox project, and we touch on the financial highlights before we go to Q&A.
Thank you, Jens. Can you please show slide number 19 from the financial summary of quarter four and the full year 2024 compared to previous year? All figures are presented in million SEK. Q4 results and cash flow align with our expectation with no significant deviations.
Revenue for the fourth quarter is approximately SEK 1 million, driven by royalty income from Xerclear. External expenses were higher than the same period last year, mainly due to increased clinical costs related to the combination study, as well as preparation for the next phase of fostrox. Personnel expenses were lower during the quarter and remain largely in line with last year for 2024. The operating loss for Q4 stands at minus SEK 27 million, exceeding last year's figure, primarily due to the clinical costs, as I mentioned. Cash flow from the operating activities in Q4 was approximately minus SEK 29 million, which was consistent with our estimates for the quarter. As of the end of December, our cash balance stands at SEK 62 million, combined with the support and the loan facility from our main shareholder Linc, we project the cash runway extending into Q4 2025 based on our current plan and assumptions.
With this, I will hand over back to Jens.
Thank you. With that, we'll stop here, and we open up the call moderator for 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. As a reminder, if you wish to ask a question, please dial pound key five on your telephone keypad. There are no questions at this time, so I hand the conference back to the speakers for any closing comments. Please go ahead.
Okay, thank you. I sort of move back to this slide, which is just a kind of walkthrough, and I'll take a very quick one again, as we tried to allude to or we've conveyed in the call today. We believe we are in a very good position to develop the first approved treatment option for patients with advanced liver cancer. We are at the moment sort of on the back of the post, sort of the IND approval by the FDA in the U.S. We are moving with as much speed as we possibly can to initiate the activities that Pia alluded to. The preparatory work for the phase II-B study or the FOcuS-2 study, as it's now named, is progressing very nicely in terms of opening and initiating the first patients in 2025 across eight countries and 40 sites.
I think one of the interesting things to kind of comment on here is that the interest by the clinical experts to participate in the study due to the significant unmet medical need in second line has been very large. We have sort of aligned on eight countries. We could have opened a number of more countries because the interest has been so big. In terms of moving with speed, but also balancing and not having too many countries, sort of we've landed on eight countries across three regions to make a proper global study in order to progress things with as much speed as we can. Unless there are any sort of questions that have popped up, I can see that there seems to be a sort of a question in the queue.
I will just stop there, moderate, and see if there is an opportunity to take a question.
The next question comes from Hans Engblom from EVM. Please go ahead. Hans Engblom from EVM. Your line is now unmuted. Please go ahead. There are no questions at this time, so I hand the conference back to the speakers for any closing comments.
Thank you.
Please go ahead.
Seems like we might have either some technical difficulties or other challenges, but sort of with regards to that, thank you all for dialing in to today's conference call. Again, we continue to see great momentum in the program in Q4. We look forward to moving forward with even greater speed in 2025 with the fostrox, fostrox Lenvima program. Thank you, everyone, for dialing in.