Medivir AB (publ)

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 FosTruxel and Vima 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 FOSTRUX development program towards initiating a pivotal phase 2b 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. And 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 talk, 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. And 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 towards the end of December. So they moved into phase one, two, 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 Erberg, our CSO, as mentioned, will go through the T&G 348 program. And Magnus will touch on the financial highlights, of course. In terms of highlights during the last quarter or the last few months, first and foremost, The post-structural and VMAR 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. And 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 and that enables us to sort of continue our acceleration activities as we move forward towards initiating a registration or face to be with accelerated approval intent. liver cancer is a challenging disease to treat and and we believe. But sort of having an organ specific targeted approach that we do have with with. Sorry, with false drugs is the key to improving clinical benefit for patients. If we look at the primary liver cancer and how it is is treated today in first line setting today, there is a standard of care and 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 types over 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 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 and 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 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. And 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 that the approach that we're taking with FosTrox is the key to the improved clinical benefit that we're seeing in the ongoing Phase 1b, Phase 2a 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. And we recently presented data from the study that Jens mentioned at Ascogia in San Francisco. And here today, we will give a following update actually at a later time point here in February 14, 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 Post-Ox Plus combination with Benzema. So the study was finally enrolled with the 21 patients. And 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. And we also allowed all grade of macrovascular invasion. And what 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 Ticentric Avastin was used in 86% of the patients. We can go to the next slide. So 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. And you can see that in the green bars to the right on this slide. And 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 Ostrox and Venema. We can go to the next slide. So how does this sort of relate to the longer term efficacy? And the improved response that we see in this study was reflected during follow-up. And we could see a durable clinical benefit. And most important here, 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, we must 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 in the 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 prognostic or predictive of what you 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 optimal response on prior treatment, would they later respond on FOSTRX? And what we can see here, now we have 6.3 months, yeah, I've 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 who had a short duration of prior treatment could actually have a longer benefit with FosTrux than Rheema. 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 we 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 FosTroc 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 FosTroc, 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 FosDrux 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 Lendvima as monotherapy. In short, the combination was tolerable, which was also shown in the previous slide, where the patient actually could stay on the treatment for a longer period of time. So we can go to the next slide. So the current result, which was just shown, showed superior efficacy compared to second line HEC. 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 HEC. We had an overall response rate of 24% where we are right now, and this should be compared with the 10% in second line HEC with current standard of care, a disease control rate of 81%, It is around 65% in standard of care. And here we have a 6.3 months of time to progression, which should be compared to 3.5 months. 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 post-trugs. And we are planning a randomized phase 2b study with a registrational intent. So 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 2 to 1, with FosTrox plus Levima versus Levima 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, we met with so many of the global experts to pressure test, is this the right way to go about a study? And 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 guidelines recommend clinical trials. 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 FTA interactions as well. So with that, over to Jens.

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 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 will, of course, sort of communicate the outcomes of those discussions. In order to have US hospitals be part of the study, we need to open an ind a so-called investigation investigation a new drug and and that will also then happen sort of after the fda type c meeting so so that's sort of well underway and what happened maybe a bit earlier what we really needed to accelerate in q4 2023 as you see on the slide is to initiate um some 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 IIb study start. And 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 and so forth. Again, we did that in 24, 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 in line with what we were planning and what we communicated sort of at the Q3 results. 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 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 that we are getting the feedback from in 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 it is a significant value opportunity as well so that is our sort of fast to market lead indication So with that, we'll move into as there's been sort of exciting news in other parts of the pipeline with regards to the partnering programs, specifically T&D 348. We will sort of touch a little bit on that. And as you see here, we do have postdocs as our in-house program that we focus our efforts to. The outlicensed programs are run by our partners without sort of further investments from our side. and the most exciting piece of news in q4 was the one community by tango so just to provide a little bit of of of an intro to what tng348 is and what they are doing at the moment frederick