Medivir AB (publ)

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 5 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. a relatively eventful time. We recently announced our intent to raise capital via a rights issue, and we're holding an extra general meeting on Monday to vote on that fully guaranteed rights issue, which is supported by our main shareholders. And 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 all four strokes in combination with Lenvima. And Pia will share much more detail on this sort of as we go through the presentation today. Pia will also talk about the latest in terms of what's 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. And then finally, we recently announced and very pleased to announce that we have signed the licensing agreement for Remitinostat, which now has the potential to generate significant value upside for the molecule moving forward. And Fredrik will... We'll share a bit more detail on what is happening and more importantly, sort of provide a bit of an update on remittance and what we see as the logical sort of steps forward for our licensing partner. So we will come back to that as well. So presenting today, apart from myself, as I've alluded to, our chief medical officer, Dr. Pia Baumann, will talk about the full structure of the project moving forward. Fredrik will touch on Remitinostat. And then Magnus, our CFO, will sort of conclude with the financial highlights as well towards the end of the call. So with that, I will hand over to Pia, and she will sort of walk through the planned phase two 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've seen in the first study with the combination of FosTrox and Lendvima. So with that, Pia.

Thank you, Jansson. You can go to the next slide. Perfect. So we left ESMO here in October. It was in Berlin, a strength 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 primordial cancer. So, coming back to this, the complete lack of prospective second-line study data at ESMA revealed again that the focus in HSE continued to be heavily shifted towards first-line advanced or earlier stages of HSE. I mean, you have all seen it, I assume, that, for example, cell therapies with CAR-Ts, ADC, targeted therapies that has been very successful in other tumor types have unfortunately not lived up to the promise in HECs. 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. So there's a gap. And with the aim of cover this gap, we have positioned the development of FosDrox in second line post immunotherapy combination, as Jens already said. And this is now reinforced in first line, evidenced also by the presentation at ESMO. And I will shortly come back to that. So our aim with FOSDROC 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 doesn't exist today. So we can go to the next slide. So several studies are trying to add a drug to immune therapy combination in order to further improve outcome in first line advanced HEC when it has failed. And here you can see in BRAVE-152, it was presented at ESMO with the experimental drug TIGIT that failed to show any benefit at all on top of T-centric Avastin. It was quite a large study. It was a phase 3 study with 669 patients, and it was randomized one-to-one in two arms. And you can see here down to the left the superimposed Kaplan-Meier problem curve of progression-free survival. So that was disappointing, but it is also entrenching the position for dyscentric Avastin in first line and a standard of care. It is a medium progression-free survival. Here it's eight months, but it has been somewhere between six and eight months in first line. And we know that all patients eventually progress. And again, why an effective second-line treatment is very much needed. And 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. so 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 and 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. And 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 hse intermediate state where it's localized in the liver when they looked at a longer follow-up overall survivor showed no significant improvement with katruda and lenvima in addition to local treatment with taste and this is the leap 012 study And the study was closed. So this again reinforces immune therapy combinations to be used in later lines, advanced HSE, and in the first line setting, which makes the strategic development of FosDrox plus Lumima in the second line post-immunotherapy setting an obvious choice. You can go to the next slide. So to support the evidence that we already have from the phase 1 A to B study with FosTrox plus Lanvima in second line advanced HEC, the next step will be a randomized comparative phase 2 study where we will enroll 80 patients with one prior immunotherapy combination. And they will receive either FosTrox 30 milligram together with Lanvima And the dose for Lenvima will be the standard weight-based doses. And 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, depending on when the response is seen. So, as previously done, imaging assessment will be done every six weeks with CT scan or MRI. And the FICAS endpoint, including the primary endpoint, which is going to be overall response rate, will importantly be evaluated by a blinded independent central review. So 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. And as Jens already said, with a rapid data readout, which is important for us in the development of OSTROX. And with the confirmation of improved efficacy that we are hoping for with FosTrox plus 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 the following registration of the study. We can go to the next slide. But 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 FosTrux plus Lenvima with the limited publication of Lenvina monotherapy in second life. So the Korean Cancer Study Group has recently finalized such a prospective study with lenvatinib or with lenvima post-immune therapy. Why this specific research consortium is the optimal one to collaborate with in the upcoming randomized phase two study. And 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. And it was very much similar to what previously had been shown with retrospective analysis of LENVIMA in second line. And 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%. And without other effective options, as we already talked about, there is nothing that is sort of suggested or aligned upon in second line. This support Lendvima use post-teccentric Avastin. And we know already from before that the clinicians prefer to use Lendvima in this setting. We can miss that. So the patients in the Korean LENVIMA monotherapy study had similar patient characteristics as the phase 1 B2A study with FosTrox plus LENVIMA. And this was, I don't 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. And when doing indirect cross-study comparison, we actually did that. We can go to the next slide. we can see that FOS drugs plus Lanvima provided substantially better outcome data compared to Lanvima monotherapy. This should, of course, be interpreted with caution, and that's why we are doing the randomized study. But here we could see that the median progression-free survival of 5.4 months When you compare that monotherapy data with lenvima to what we saw with FosTrox plus lenvima, time to progression was 10.9 months. The response rate was 14% with the lenvima mono. We had 24% with FosTrox plus lenvima in this study. And the median overall survival of 9.8 months in the phase 1b2a study was 13.7 months with FosTrox plus lenvima. So this is encouraging, really encouraging for the future development of OSTROX. And 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. So 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. But with that, we will move forward with regards to today's program, and we'll go into the third part, which is the outlicensing of Remitinnostat and the potential that it provides. So before handing over to Fredrik, just a couple of notes to make. It is an exclusive sort of global licensing agreement that we've made with a Canadian US based company called BioSil. And in the discussions with them, that has sort of focused to some extent on the phase two data that has been shown the positive data in in ctcl but perhaps even more so in the basal cell carcinoma space so in terms of moving forward that tech transfer has been initiated we have connected them with the investigators from the studies uh already and 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 sort of approximately 60 million US dollars. so that the key value upside comes from the royalty and potential royalty stream and or also sort of there is a sub-licensing revenue share in case they develop it further and then they want to sort of sub-license it to someone else. We have gotten question whether there was an upfront involved and 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. But with that, just sort of a kind of quick recap and reminder on Remetinnostat and what then might be sort of the path forward for our partner. Fredrik?

Thank you, Jens. So at Medivir, we're really excited that the Remitinostat project moves on in its clinical development. As you may remember, Remitinostat is an histone deacetylase inhibitor, HDAC inhibitor, designed to be applied by a gel topically to skin cancers. And this, you might think, is very, very different from FosTrox, but from a cancer biologist's 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. So it's especially suitable for skin cancers. And as Jens mentioned, it's 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. And here comes the treatment in the right place concept to be a very important aspect of the rematinostat molecule. And the rematinostat molecule solves this in a very elegant way. So 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. So if you look at the central panel there, there's a stability in the skin where it's 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 of the treatment efficacy. And we can see that in skin, these are biopsies on the right-hand panel, data from cutaneous T-cell lymphoma in the phase one study. treated with remitinostat 1% twice daily, you see an increase in acetylation. That's the response that you expect when you inhibit the deacetylase enzyme. So it works, it's de-risked, and it's been in three different types of tumors in clinical trials. So if we look at the next slide, good results in cutaneous T-cell lymphoma, It completed a phase two open label dose selection study, and it had a good response, 40% confirmed overall response rate, objective response rate, and the median duration of seven months. And it was a selection then of a phase three dose for this indication. Also a study in basal cell carcinoma, a phase two 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 and no serious systemic adverse events reported. and 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. So 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, and we hope to see more in the clinical development. But 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 the topical gel. At eight weeks, the tumor was surgically removed and a pathologic evaluation was done. So we see here across different histological subtypes, which are more or less severe. an overall response rate of about 70%. And if you look at the pathological response, more than half of them had a complete pathological resolution. So, as Jan said, we've introduced the BioSeal team to investigators in all these different tumor types or indications that have been tested, and we're really looking forward to watching the progress in clinical development because it's a really, really elegant concept and a de-risked type of treatment. So with that, Jens. We move forward.

Yep. And then we sort of pivot to the financials in terms of Q3 highlights. So Magnus.

Okay. Thank you, Jens. Yes. This is slide number 23. And we can see the financial summary for Q3 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 the 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 one 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 14, improved from last year and primarily driven by the lower clinical costs and including CMC related costs. Cash flow from the operating activities in the quarter was around 14 also, consistent with our estimates, and substantially lower compared to the same period last year and previous quarters this year. And at the end of September, our cash balance was approximately 24, and together with the planned fully guaranteed right issue that Jens mentioned, We project the cash runway until the end of 2027. And with that, I hand back over to Jens.

Thank you, Magnus. So 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 Reme Timmestad. with the opportunity of realizing the potential value for the molecule moving forward. So as Fredrik indicated, we look forward to seeing that further development. And two, we are currently moving with as much speed as we possibly can with the aim of generating the comparative and robust data to support or confirm in in a comparative study the the common benefit of the combination for structures lenvima with the korean group and and with the aim of generating that data as rapidly as we possibly can so with that we stop and we move to q a

If you wish to ask a question, please dial pound key 5 on your telephone keypad. To enter the queue, if you wish to withdraw your question, please dial pound key 6 on your telephone keypad. The next question comes from Richard Romanius from Red Eye. Please go ahead.

Good afternoon. I have a few questions. Let's start with the BioSil deal. Okay, let me just frame the first question like this. If I assume that BioSil will develop rematinostat in basal cell carcinoma only for the US market, do you think that would be a reasonable modeling assumption?

I think it has a much broader, I mean, sort of the Gorlin syndrome patient population is not a, there's not a specific US population that you will see equal numbers in other countries. We have, 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 Gordland Syndrome Centre in Manchester, which is among the key opinion leaders that we've been asked to connect Biasil with. So I wouldn't see this from a modeling perspective as a U.S. only, a sort of potential upside. And from a commercial upside perspective, there is clear value outside of the U.S. as well. Might be that it's bigger in the U.S., but I wouldn't rule out X U.S., no.

Okay, good. A quick question. How much, could you say... how much goes to Tetra Logic?

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, the single digit that I would say. But you will probably can do the calculation when you see the Q4 report.

Yeah, OK. Could you say something about the remaining IP protection for rematinostate?

The remaining IP protection is not the longest. I'm looking at Fredrik in terms of what the date is, but I think that what I will say is that it actually hasn't been a focus from a Biosil perspective. That was sort of clear from the get-go. The reason why they were attracted is that they see the upside in the in the sort of orphan drug rare disease space like Gordlin syndrome and other populations because that provides additional protection beyond the loss of patent timelines. So they will focus their protection on orphan drug and data exclusivity and 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 four strokes after you get the phase two data? Will you proceed with a phase three trial and do you think you'll do that with a partner?

I think that is an excellent question and depending on the data hopefully it will be as good as we think it will be. There are several alternatives and I'm sure that you are aware that sort of the development is not anymore just phase one phase two phase three there's possibility to do different adaptive design and so on so i think i need to answer your question a little bit like it depends on the data and obviously it depends on how much the investors are willing to invest in the project and we will try to find a design or a solution that makes a 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's a huge interest and the trial design that is most supporting in getting this approved as soon as possible.

And the add from my end Richard is and I think that we've communicated sort of when we announced the The rights issue. Do we see ourselves bringing FosTrux to the market on our own and 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 and and in those discussions there there has been i think as we we tried to sort of be reasonably clear on in in the launch of the rights issue there has been sort of one question that has sort of has been the the front of mind and that is uh yes the liver targeted approach is highly attractive and yes the data that we've seen in the phase one v2a study is is quite encouraging the and and 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. So there has been sort of that uncertainty regarding what is Fostrox adding, and that provides for a sort of a perceived clinical risk. So that the steer has been, and the feedback we've gotten is that we 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 in one study and i think that's been in before we can value the molecule properly or value the molecule as as you are are probably valuing it but sort of following 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. And with that, we think that 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. So 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 and 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. the ability to generate cell death in tumor cells only, but sparing healthy liver cells. The data that we've generated in the first study as 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 sort of 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. And that's why 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. But 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 so we can generate the comparative data to confirm the benefit of adding FosTrox to Lenvima and 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. So 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. So with that, thank you everyone for dialing in and listening and have a good rest of the day.