Welcome to Medivir Q3 Report 2025. For the first part of the conference call, the participants will be in listen-only mode. During the questions-and-answers 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 our sort of Q3 Report 2025 at Medivir. We will focus on three things today as we go through the recent quarter and as we look ahead to the next steps. Relatively eventful time. We recently announced our intent to raise capital via a rights issue, and we are holding an extra general meeting on Monday to vote on that fully guaranteed rights issue, which is supported by our main shareholders. This rights issue will enable us to take a major step forward with our lead asset, or with our main project, fostrox, in order to generate robust and randomized data in a rapid fashion to confirm the benefit of fostrox in combination with Lenvima. Pia will share much more detail on this sort of as we go through the presentation today.
Pia will also talk about sort of the latest in terms of what is happening in the primary liver cancer space. We recently visited ESMO Congress, and what we can conclude, which Pia will also talk about, is the design of the study, the positioning of fostrox sort of continues to align well with the significant unmet medical need in second-line liver cancer. Finally, we recently announced, I am very pleased to announce, that we have signed a licensing agreement for Remetinostat, which now has the potential to generate significant value upside for the molecule moving forward. Fredrik will share a bit more detail on what is happening and, more importantly, sort of provide a bit of an update on Remetinostat and what we see as the logical sort of steps forward for our licensing partner. We will come back to that as well.
Presenting today, apart from myself, as I have alluded to, our Chief Medical Officer, Dr. Pia Baumann, will talk about sort of fostrox and the project moving forward. Fredrik will touch on Remetinostat. Magnus, our CFO, will sort of conclude with the financial highlights as well towards the end of the call. With that, I will hand over to Pia, and she will sort of walk through sort of the planned phase II study, which we are raising capital for, and sort of how that will enable rapid generation of randomized and comparative data to confirm the benefit that we have seen in the first study with the combination of fostrox and Lenvima. With that, Pia.
Thank you, Jens. You can go to the next slide. Perfect. We left ESMO here in October. It was in Berlin. Strengthened in our belief that there's definitely still a high need for an effective treatment in the second-line advanced liver cancer. Or actually, we will call it HCC. You will see it on this slide because it's an abbreviation of hepatocellular carcinoma, which is the most common form of primary liver cancer. Coming back to this, the complete lack of prospective second-line study data at ESMO revealed again that the focus in HCC continued to be heavily shifted towards first-line advanced or earlier stages of HCC. I mean, you have all seen it, I assume, that, for example, cell therapies with CAR-Ts, ADC, targeted therapies that have been very successful in other tumor types have unfortunately not lived up to the promise in HCCs.
It might be the lack of actionable targets in the majority of the patients and the comorbidity with liver dysfunction causing tolerability challenges. That is the main reason. There is a gap. With the aim of covering this gap, we have positioned the development of fostrox in second-line post-immunotherapy combination, as Jens already said. This is now reinforced in first-line, evidenced also by the presentation at ESMO. I will shortly come back to that. Our aim with fostrox is very much supported also by the global experts and overall the HCC community that is very eager to have in their hands an alternative when the patients progress in first-line. That does not exist today. We can go to the next slide.
Several studies are trying to add a drug to immunotherapy combination in order to further improve outcome in first-line advanced HCC when it has failed. Here you can see in IMbrave152 , it was presented at ESMO with the experimental drug TIGIT that failed to show any benefit at all on top of Tecentriq + Avastin . It was quite a large study. It was a phase III study with 669 patients, and it was randomized 1:1 in two arms. You can see here down to the left, the superimposed Kaplan-Meier curve of progression-free survival. That was disappointing, but it is also entrenching the position for Tecentriq + Avastin in first-line and a standard of care. It is a median progression-free survival. Here, it is eight months, but it has been somewhere between six and eight months in first-line. We know that all patients eventually progress.
Again, why an effective second-line treatment is very much needed. Here to the right, you can see part of a treatment guideline, and it still suggests a clinical trial as the best option in this patient population due to the fact that there are no results from second-line studies with this setting that we have today. You can go to the next slide. The current trend in oncology overall is to use systemic therapy in earlier stages of disease and aiming for a curative treatment, also when it is a little bit more advanced than sort of the early stages. This has also been tested in HCC with somewhat disappointing results. A couple of years ago, they suggested to use adjuvant systemic treatment after surgery, and it failed to show any benefit.
While seeing early signs of promising effect, looking at progression-free survival that you see here to the left, with immunotherapy in an earlier stage of HCC, intermediate stage where it is localized in the liver. When they looked at a longer follow-up, overall survival showed no significant improvement with Keytruda and Lenvima, in addition to local treatment with TACE. This is the LEAP-012 study. The study was closed. This again reinforces immune therapy combinations to be used in later lines, advanced HCC, and in the first-line setting, which makes the strategic development of fostrox + Lenvima in the second-line post-immunotherapy setting an obvious choice. You can go to the next slide.
To support the evidence that we already have from the phase I-A/II-B study with fostrox + Lenvima in second-line advanced HCC, the next step will be a randomized comparative phase II study where we will enroll 80 patients with one prior immunotherapy combination. They will receive either fostrox 30 mg together with Lenvima. The dose for Lenvima will be the standard weight-based doses. It will be randomized against Lenvima as monotherapy. This will be done at eight sites as part of the Korean Cancer Study Group that we are collaborating with. Enrollment is estimated to 12 months, and primary endpoint follow-up will be between three and six months, dependent on when the response is seen. As previously done, imaging assessment will be done every six weeks with CT scan or MRI.
The efficacy endpoint, including the primary endpoint, which is going to be overall response rate, will importantly be evaluated by a blinded independent central review. The collaboration with an established research consortium as the Korean Cancer Study Group will also ensure that we will generate robust comparative efficacy and safety data. As Jens already said, with a rapid data reduction, which is important for us in the development of fostrox. With the confirmation of improved efficacy that we are hoping for with fostrox + Lenvima compared to Lenvima alone. In this randomized setting that we will have in this study, we will use this data to make a more accurate assumption that will actually strengthen the design on a following registration of the study. You can go to the next slide. We are not there yet, right?
Before we have head-to-head data, we have been, and we will be, reliant on comparing the data we have for fostrox + Lenvima . With the limited publication of Lenvima monotherapy in second-line. The Korean Cancer Study Group has recently finalized such a prospective study with Lenvima post-immunotherapy. Why this specific research consortium is the optimal one to collaborate with in the upcoming randomized phase II study. The Lenvima monotherapy study enrolled 50 patients at 13 sites, and the efficacy was shown to be superior to other TKI, not in this study, but if you compare. It was very much similar to what previously had been shown with retrospective analysis of Lenvima in second-line. Here you can see a median progression-free survival of around 5.4 months, median overall survival 9.8 months, and an overall response rate of 14%.
Without other effective options, as we already talked about, there is nothing that is sort of suggested or aligned upon in second-line. This supports Lenvima use post-Tecentriq + Avastin. We know already from before that the clinicians prefer to use Lenvima in this setting. You can go to the next slide. The patient in the Korean Lenvima monotherapy study had similar patient characteristics as the phase I-B/II-A study with fostrox + Lenvima . This was, I do not know if you can see this, but it was very much the age, gender, liver function, if it was viral, non-viral, AFP levels, and prior systemic and local treatments. When doing indirect cross-study comparison, we actually did that. We can go to the next slide. We could see that fostrox + Lenvima provided substantially better outcome data compared to Lenvima monotherapy.
This should, of course, be interpreted with caution, and that's why we are doing the randomized study. Here we could see that a median progression-free survival of 5.4 months, when you compare that monotherapy data with Lenvima to what we saw with fostrox + Lenvima , time to progression was 10.9 months. The response rate was 14% with the Lenvima monotherapy. We had 24% with fostrox + Lenvima in this study. The median overall survival of 9.8 months in the phase I-B/II-A study was 13.7 months with fostrox + Lenvima . This is encouraging, really encouraging for the future development of fostrox. I will leave it back to Jens to continue talking about this.
The added comment on this particular study is that the Korean group were able to recruit patients very, very quickly. Again, encouraging with regards to moving forward in collaborating with this particular group, as clearly one of the elements that we're trying to achieve with the next study is to move forward with as much speed as possible so that we can move into a registrational phase as soon as possible. With that, we will move forward with regards to today's program. We'll go into the third part, which is then sort of the outlicensing of Remetinostat and the potential that it provides. Before handing over to Fredrik, just sort of a couple of notes to make. It is an exclusive sort of global licensing agreement that we've made with a Canadian-U.S.-based company called Biossil.
In the discussions with them, that has sort of focused to some extent on the phase II data that has been shown, the positive data in CTCL, but perhaps even more so in the basal cell carcinoma space. In terms of moving forward, that tech transfer has been initiated. We have connected them with sort of the investigators from the studies already, and they've sort of shared their eagerness to move forward from a development perspective. It is. In terms of financials, sort of as communicated, sort of the total potential milestone payments sort of make up to approximately $60 million. The key value upside comes from the royalty and potential royalty stream and/or also sort of there is a sublicensing revenue share in case they develop it further and then they want to sort of sublicense it to someone else.
We have gotten questions whether there was an upfront involved. A deal like this is usually quite backloaded, and this one is as well. There was an upfront of more minor character, and we haven't disclosed the value, but you will also see it in our quarter four quarterly report. With that, just sort of a kind of quick recap and reminder on Remetinostat and what then might be sort of the path forward for our partner, Fredrik.
Thank you, Jens. At Medivir, we're really excited that the Remetinostat project moves on in its clinical development. As you may remember, Remetinostat is a histone deacetylase inhibitor, HDAC inhibitor. Designed to be applied by gel topically to skin cancers. You might think this is very, very different from fostrox, but from a cancer biologist point of view, it has many similarities. You treat where the tumor is. You treat here the skin cancer, or in fostrox's case, you treat the liver. It is especially suitable for skin cancers. As Jens mentioned, it has been tested in clinical trials, both in cutaneous T-cell lymphoma, basal cell carcinoma, and squamous cell carcinoma, cutaneous squamous cell carcinoma, with good results. Now, this class of inhibitors, HDAC inhibitors, there are FDA-approved such for the treatment of some of these tumor types. They are, unfortunately, very burdened by toxic effects.
Systemic toxic effects. Here comes the treatment in the right place concept. To be a very important aspect of the Remetinostat molecule. The Remetinostat molecule solves this in a very elegant way. If we look at the next slide. On the left panel, the topical application inhibits histone deacetylase enzymes in the tumor. In the skin. Where the molecule that reaches the bloodstream is very, very rapidly broken down to two innocuous compounds that have no toxicities. If you look at the central panel there, there is a stability in the skin where it is rapidly, rapidly broken down in blood. This means that you can apply it to the tumor on skin without the systemic side effects of other HDACs. The fact that other HDAC inhibitors have been approved also sort of de-risks the concept or the treatment efficacy.
We can see that in skin, these are our biopsies on the right-hand panel. Data from cutaneous T-cell lymphoma in the phase I study. Treated with Remetinostat 1% twice daily. You see an increase in acetylation. That is the response that you expect when you inhibit the deacetylase enzyme. It works. It is de-risked. It has been in three different types of tumors in clinical trials. If we look at the next slide, good results in cutaneous T-cell lymphoma. It completed a phase II open-label dose selection study. It had a good response, 40% confirmed overall response rate, objective response rate, and a median duration of seven months. It was a selection then of a phase III dose for this indication. Also, a study in basal cell carcinoma, a phase II study. Open-label, single-arm .
Where there was a significant decrease in tumor burden after six weeks of treatment. A large majority reaching complete pathological resolution. No serious systemic adverse events reported. A smaller study in cutaneous squamous cell carcinoma, where there was also 100% complete clinical and pathological resolution of the few tumors that were able to be evaluated. This was during the COVID-19 pandemic. We think that if we look at the next slide, just an example from the basal cell carcinoma study, there are certain aspects that are really encouraging. We hope to see more in the clinical development. If we look at the basal cell carcinoma responses here, we see clearly that many different histological subtypes are responding well. These are patients; they were treated six weeks with a topical gel. At eight weeks, the tumor was surgically removed, and a pathologic evaluation was done.
We see here across different histological subtypes, which are more or less severe. An overall response rate of about 70%. If you look at the pathological response, more than half of them had a complete pathological resolution. As Jens said, we have introduced the Biossil team to investigators in all these different tumor types or indications that have been tested. We are really looking forward to watching the progress in clinical development because it is a really, really elegant concept and a de-risked type of treatment. With that, Jens.
We move forward. Yep. And then we sort of pivot to the financials in terms of two, three highlights. So Magnus.
Okay. Thank you, Jens.
Yes. This is slide number 23. We can see the financial summary for quarter three this year and year-to-date September. Compared to previous year. And all numbers are million SEK as normally. As we mentioned in the Q2 report call, we expect the lower cost and improved cash flow in Q3, which is really reflected in the results, as you can see. Both the Q3 results and cash flow were in line with our expectation and with no material deviations. Revenue for the third quarter is approximately SEK 1 million, which is in line with last year for the quarter and year-to-date. External expenses were significantly lower in Q3, as anticipated, mainly due to reduced clinical costs compared to last year and previous quarters. The operating loss for Q3 was around SEK 14 million. Improved from last year and primarily driven by the lower clinical cost and including CMC-related cost. Cash flow from the.
Operating activities in the quarter was around SEK 14 million also, consistent with our estimates, and substantially lower compared to the same period last year and previous quarters this year. At the end of September, our cash balance was approximately SEK 24 million. Together with the planned fully guaranteed rights issue that Jens mentioned, we projected cash runway until the end of 2027. With that, I hand back over to Jens.
Thank you, Magnus. Just to kind of repeat before we go to Q&A, we are super happy that we have been able to find a good home for Remetinostat with the opportunity of realizing the potential value for the molecule moving forward. As Fredrik indicated, we look forward to seeing that sort of further development. We are currently moving with as much speed as we possibly can.
With the aim of generating the comparative and sort of robust, sort of data to support or confirm, in a comparative study, the benefit of the combination fostrox + Lenvima with the Korean group and with the aim of generating that data as rapidly as we possibly can. With that, we stop 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.
Good afternoon. I have a few questions. Let's start with the Biossil deal. Okay. Let me just frame the first question like this. If I assume that Biossil will develop Remetinostat in basal cell carcinoma only for the U.S. market, do you think that would be a reasonable modeling assumption?
I think sort of it has a much broader—I mean, sort of the Gorlin syndrome patient population is not a—there's not a specific U.S. population. Sort of you will see equal numbers in other countries. In our discussions, which we've had with external experts. We've had those discussions with experts from Europe as well. There's a very sort of large Gorlin syndrome center in Manchester, which is among the key opinion leaders that we've been asked to connect Biossil with. I wouldn't see this from a modeling perspective as a U.S.-only sort of potential upside. From a commercial upside perspective, there is clear value outside of the U.S. as well. It might be that it's bigger in the U.S., but I wouldn't rule out ex-U.S. No.
Okay. Good. A quick question. How much could you say? How much goes to TetraLogic?
The short answer is no in the sense that we haven't disclosed the percentages of the revenue share. Now I'm looking at Magnus in terms of have we provided any.
No. I mean, the guidance will be it's not single digits. It's more material than single digit that I would say. You probably can do the calculation when you see the Q4 report.
Yeah. Okay. Could you say something about the remaining IP protection for Remetinostat?
The remaining IP protection is not the longest. I'm looking at Fredrik in terms of what the date is. I think that what I will say is that it actually hasn't been a focus from a Biossil perspective. That was sort of clear from the get-go. The reason why they were attracted is that they see the upside in the sort of orphan drug rare disease space like Gorlin syndrome and other populations because that provides additional protection beyond the loss of patent timelines. They will focus their protection on orphan drug and data exclusivity. They will also be exploring alternative ways to extend patent via formulation work, etc., so that the patent life on the molecule itself is not going to be super relevant for their development and not going to be super relevant for.
Any modeling of the value of the molecule either.
Okay. That's good to know. My last question. What is the plan with fostrox after you get the phase II data? Will you proceed with a phase III trial? And do you think you'll do that with a partner?
I think that is an excellent question. Depending on the data, hopefully, it will be as good as we think it will be. There are several alternatives. I'm sure that you are aware that sort of the development is not anymore just phase I, phase II, phase III. There is possibility to do different adaptive design and so on. I think I need to answer your question a little bit like it depends on the data. Obviously, it depends on how much the investors are willing to invest in the project. We will try to find a design or a solution that makes it as fast as possible to the market because what we are fully aware of and we hear over and over again is that there is huge interest and the trial design that is most supporting in getting this approved as soon as possible.
The add from my end, Richard, is—I think that we've communicated sort of when we announced the rights issue. Do we see ourselves bringing fostrox to the market on our own and sort of commercializing it? I don't think that's the most realistic path forward. We've had many discussions with potential partners, and we continue to have discussions with potential partners and investors. In those discussions, there has been—I think as we tried to sort of be reasonably clear on in the launch of the rights issue—there has been sort of one question that has sort of been the front of mind. That is, yes, the liver-targeted approach is highly attractive. Yes, the data that we've seen in the phase I-B/II-A study is quite encouraging. Moving forward into a larger randomized comparing with Lenvima is the right sort of strategic move.
The key question has been sort of what is fostrox adding on top of Lenvima, considering that it's been a single-arm study. There has been sort of that uncertainty regarding what is fostrox adding, and that provides for a sort of a perceived clinical risk. The steer has been, and the feedback we've gotten is that we would like to continue to have the discussion. We very much want to sort of follow what you're doing. We would like to see comparative data in one study. I think that's been before we can value the molecule properly or value the molecule as you are probably valuing it. Hence the need to move and generate that data, generate comparative data from a randomized study, and to do it with as much speed as we possibly can. With that.
We think that sort of you can never promise anything, but clearly, we believe that. The value of that data will make those discussions with potential partners and investors very different than it has been on the back of the single-arm data.
Yeah. I think that makes sense. Thanks for taking my questions.
There are no more questions at this time. So I hand the conference back to the speakers for any closing comments.
Thank you. I'll just kind of circle back to this slide, which we have shown before, and sort of try to sort of sum things up. To highlight in terms of what we're doing and why we're doing it. Sort of as mentioned, we've had numerous discussions, sort of many, many discussions with potential partners and investors where we've gotten sort of quite sort of strong interest on the approach, which we highlight up on the left-hand side, sort of the ability to generate cell death in tumor cells only, but sort of sparing healthy liver cells. The data that we've generated in the first study, as sort of Pia showed before and as you see on the panel top right, is quite encouraging with a time to progression of 10.9 months versus the four to five months we see with current available treatments.
There is a clear unmet medical need. There are no approved treatments in second line. There's still the opportunity to move with speed and become that sort of first-to-market opportunity. That's why, sort of, we're very happy to collaborate with the Korean group because with the Korean group, we know that we can run the planned study of 80 patients in sort of rapid fashion. More importantly, they are highly experienced in the second-line space. They will be able to generate that data in a very sort of qualitative and robust way. We can generate the comparative data to confirm the benefit of adding fostrox to Lenvima. Hopefully then, moving forward, sort of on the back of that data to still take the place as the first approved treatment option in second-line liver cancer, which there still clearly is opportunity for.
We are very much looking forward to running the project with the Korean group and starting it in early 2026 to initiate patients and to see the data from that study coming out in 2027. With that, thank you, everyone, for dialing in and listening, and have a good rest of the day.