Medivir AB (publ)

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. We, quarter four last year, continued to be a good quarter with regards to momentum in our primary program, FosTrox, which is our sort of oral liver targeted treatment in development for advanced liver cancer. We closed our Phase 1b, Phase 2a study of Fostrox in combination with Lenvima, and we are very much looking forward to presenting the final data at the EAS 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. But we closed the study in November with three patients transitioning to compassionate use. And we'll provide an update on that, those patients as well, when we get to EASL on Thursday. Importantly, as we look ahead to the planned Phase 2b study, which now has a name, which is the FOCUS 2 study, we got IND approval of that study by the FDA in quarter four. And so they've approved the study design, and that's 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. And then thirdly, as we've communicated previously, we have agreed on a clinical collaboration and supply with ACI and that collaboration is ramping up and we've established a joint development committee. So moving forward with that and also then progressing plans quite quickly outside of the US looking ahead to into 2025. So 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 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 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. But moving into looking at sort of FosTrux program, as mentioned, we continue our phase 2b study initiation sort of progress. And we've also in Q4 sort of seen data presented at ESMO Asia that confirms the FosTrux-Lenvima combination clinical benefit that we've seen previously. And I'll hand it over to Pia to walk through the two different topics.

super thank you very much and i'll continue a little bit on uh where we are right now and what is happening post ind approval uh the nd approval was given for and i will continue to call this study now the study that we are planning the phase 2b for the focus 2 study And 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 Fostros 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. And this study is really powered to show a clinically meaningful difference between FOSTRAS plus Lendema versus Lendema monotherapy. So this is sort of the base for where we are right now. We can go to the next slide. So a little bit more in details then. So as I said, FOSTROS 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 the study results show a little bit similar that we have seen in the Phase 1b2a 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. And in the first part, as you can see here, part one, the patients will be randomized to three arms, one with FosRox 10 milligram plus Lanvima, The other one with FosTrox 30 mg plus Lenvima and one arm with only Lenvima. And this first part, the enrollment period for enrolling these 60 patients is assumed to be 12 months. And 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. And this dose selection is made by an independent board that is not associated with us or with the study. And 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. And 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 landina alone so and in this process the deselected arm will be dropped the enrollment in part two is also estimated to take 12 months but then we hope to have all the 40 sites in eight countries opening and participating so 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 inform we can go to the next slide So 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 US 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. Okay, good. Next slide. So with the IND approval, the focus to activities that are really crucial for study opening are progressing very nicely with the key start-up activities that you see on this slide, which includes site selection finalization, obviously, an initiation of the contract for the sites, the different regulatory and ethics committee submissions in the countries, We have also important, the study set up collaboration with the SAI, which includes the Lenvima supply. And then we need to have all the supply of the study drives ready at the sites, which includes false drugs and also placebo, and all the different systems set up for data capture, et cetera. So this is really what we are doing currently right now, and it's progressing nicely. And we can go to the next slide. So in all this, there's a lot of assumptions, right? And so to further support our assumptions, we are monitoring everything that is going on. And 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. But our assumptions is sort of built on what we can see with Lenvima alone. And the first prospective actually study that has been presented was presented at ESMO Asia in 2024. And we looked at this study. It was from Korea, 13 sites. It was a multi-center study that enrolled 50 patients. And they received Lenvima after Tocentric Avastin. It was very much a similar patient population that we had in our phase one B2A study with FosTrox plus Leuvena. So 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. Yeah, I've already gone to the next slide. So far. 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. And again, prospective studies with Lanvima monotherapy, post and IO is scary. This is the first one that we have seen. So we can go to the next slide. So the outcome data from this study, from this Lenvima monotherapy study, really confirmed what has been shown previously. And I'm 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 medium progression-free survival of 5.4 months with a median overall survival of 8.6 months. But it pretty much is similar to what we have seen before and was really confirmatory. So if we do this nice indirect comparison, which we always do, between Lanvima monotherapy And the phase 1b2a study with FosTrox plus Lendvima, there was a substantially longer time to progression, as you can see here, between what you see with FosTrox Lendvima with a medium time to progression of 10.9 months and compared with what we already looked at, this 5.4 months with Lendvima model therapy. And 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? And this might seem like a little detail, but it's really important when it comes to understanding the progression, because the more often you do an assessment, the earlier you will identify the progress. So in the study that we are comparing with, it was with eight weeks interval and in the phase one, phase one V2A started with FOSTRAS plus Lanvirma. We actually did both CT scans and MRI every six weeks. So we feel pretty confident with this data. Next slide. And Jens already talked about this, so we are super excited to present data at ESL Liver Cancer Summit, and it's on Thursday. And if you can read these 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 important, we will have a final update on safety and tolerability. So stay tuned. And I hope that you will sort of see some of this data. Otherwise, you can look at our website later. So I will give it back to Jens.

Thank you. Then we can sort of compare the overall survival we show then on Thursday with what we saw from the prospective Lendvima data from ESMO Asia. As Pia alluded to, sort of one thing that we look at sort of continuously is we sort of try to find sort of 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 sort of at the forefront of development in second line. There's very few drugs in development for second line liver cancer. We've, as we explore the treatment algorithm in advanced liver cancer, we can see that it's established in first-line treatment that immunotherapy combination is used, primarily to centric 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. So quite a few studies ongoing in first line. But if you look on the left side, if you move down to second line treatment, there are, as we've concluded before, there are no approvals after immunotherapy combination in first line. There is a lack of scientific evidence as to what actually works in second line. So 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 Linvima, which is one of the reasons why we've combined with Linvima. But in many countries, it's not allowed and it's not funded. So it poses a challenge for physicians. for physicians. We've recently had the big GI, Gastrointestinal Cancer Congress in the US, in San Francisco, ASCO GI in January. There is the EASL Liver Cancer Summit taking place this week in Paris. And we can summarize those congresses by concluding, again, there is very little development in second line. So, we've been sort of strengthened in our conviction that we are, with the FosTroc-Lenvima combination, we are 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 to study as quickly as we possibly can. And 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. And what we see with patients that are obese, more than, for example, take the US example, 45% of adults obese, more than 25% have fatty liver disease. And among other things, a study at Karolinska have shown that if you have fatty liver disease, the risk of getting liver cancer is 17-fold. So it's a dramatically increased risk when patients have a fatty liver disease. And the number of patients who will be incurring fatty liver disease in the coming decade is anticipated to grow quite rapidly. so a significant unmet need and a large commercial potential so 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 and 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 and as pia shown the data we've shown is is very competitive and shows a very strong clinical benefit compared to what can be expected with today's available treatments. So 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. And conservatively going down to the bottom right, And that market, when we get to 2030, will be valued at least two and a half billion U.S. dollars annually. And that's likely a conservative estimate that could be as much as sort of three to $4 billion, depending on on sort of the amount of patients with fatty liver disease that then grows and develops liver cancer. So a significant commercial potential. So with that, I think we stop in terms of progress on the FOSSTROX project and we touch on the financial highlights before we go to Q&A.

Thank you Jens. Can you please show slide number 19? Not too much the summer of Q4 and the full year 2024 compared to previous year. All figures are presented in million SEK. The Q4 results and cash flow aligned with our expectations with no significant deviations. Revenue for the fourth quarter is approximately one, driven by royalty income from Seclear. External expenses were higher than the same period last year mainly due to increased clinical costs related to the accommodation study as well as preparation for the next phase of FOSTOPS. Personnel expenses were lower even a quarter and remain large in line with last year for 2024. The operating loss for Q4 stands at minus 27, exceeding last year's figure, primarily due to the clinical costs, as I mentioned. And cash flow from the operating activities in Q4 was approximately minus 29, which was consistent with our estimates for the quarter. And so the end of December, our cash balance stands at 62. Combined with the support and the loan facility from our main shareholder Link, we project the cash runway extending into Q4 2025 based on our current plan and assumptions. And with this, I will hand over back to Jens.

Thank you. And 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. Then 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 it 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 for patients with advanced liver cancer. And we are at the moment sort of on the back of the post sort of the IND approval by the FDA in the US. We are moving with as much speed as we possibly can to sort of initiate the activities that Pia alluded to. preparatory work for the phase to be study or the focus to study, as it's now named, is progressing very nicely in terms of sort of opening in and initiating the first patients in 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 this study due to the significant medical need, the second line has been very large and we have sort of aligned on eight countries we could have opened a number of more countries because the interest has been so big but in terms of moving with speed but also balancing and not having too many countries so that we've landed on on eight countries across three regions to make a proper global study in order to progress things with much speed as we can so unless there are any any questions that have popped up I can see that there seems to be a sort of a question in the queue so I'll just stop there moderate and see if there's there is an opportunity to take a question

The next question comes from Hans Engblom Engblom from EVM. Please go ahead. Hans Engblom 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.

Seems like we might have either some technical difficulties or other challenges. But with regards to that, thank you all for dialing into 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. So thank you, everyone, for dialing in.