Medivir AB (publ)

Thank you and good afternoon, good morning everyone to the Medivir Q3 report. We are thrilled to sort of walk you through sort of the events of the past quarter. We've seen a lot of progress in our lead asset FosTrox and especially over the last couple of weeks. So we look forward to going through the the bigger events as we aim to bring the first oral liver targeted treatment for patients with advanced liver cancer to market. In terms of key events during the past quarter, as we have presented earlier, in September at the ESMO Congress, we presented the mature data set from an efficacy point of view, confirming the promise of improved outcome of the combination with FosTrox and Lenvima. showing, among other things, a 10.9 months sort of mature data set with regards to time to progression, sort of substantially longer than what can be expected with current treatment alternatives in second line. further strengthening our belief in the combination as a treatment option for the future. Pia will go through in a bit more detail what we shared at ESMO and feedback we received from the scientific community, etc. Secondly, and importantly earlier this week, we were able to announce the clinical trial collaboration that we have now sort of signed with ASI, so they're further validating the potential sort of for the combination of Foss-Struxel and Vima. As part of this agreement, and we'll talk about that a little bit sort of further, we will sort of form a joint development committee with ASI And we are very pleased to be sort of working with them moving forward while still retaining the full rights to the asset. And thirdly, and equally importantly, we had our monotherapy data published in the Journal of Hepatocellular Carcinoma, sort of highlighting to the world the proof of concept of Fostrox as a liver targeted treatment for cancer in the liver. So it's been a good quarter. In the room with me today, apart from myself, Dantzler Pia Malmann, our chief medical officer, will be going through some of our experience and data from ESMO. And part of the Q&A, and Magnus will, of course, as our CFO, go through the financial highlights. And Fredrik Öberg, our CSO, is with us in the room for the Q&A session as well. So with that, let's look back and take us back a couple of months to the exciting data presentations that we had at ESMO. Pia?

Thank you. So we now have mature data. We have in this study that was presented at ESMO a median time of follow-up of 10.5 months. And this is the combination with Fostrox and Lenvima. And as Jens already said, we presented it and it really confirms what we have shown before about the promise of efficacy. so we can go to the next slide so uh at esmo and the data that was presented there i'll just start to say overall mainly focused on first-line treatment in advanced liver cancer and one of those who presented this pointed really out that there are now eight different regimens in the first line setting and none of those who were there really know what to do after, why the focus should really be on second line treatment and beyond. And one of the investigators in our ongoing study, Dr. Shon from Korea has certainly focused on second line and have recently in several publications provided data, real-world data from his clinic for Lenvima's monotherapy in second line. So, in order to put our data that we have presented at ESMO, but also at ESMO-GI, from FosTrox in combination with Lenvima, into the context, we invited Dr. Jean-Thor Webex during ESMO, which some of you attended. where he shared his experience from treating patients with LEMVIMA as monotherapy at his clinic and compared those data with the outcome on patients treated with FOSTRUX plus LEMVIMA in our study. So, just as a reminder, I know we have shown this before, the FosDrox plus Lenvima study consisted of first the dose escalation part, followed by dose expansion part, where we ended up in the dose of 30 mg FosDrox that is taken orally once daily for five days in the 21-day cycle. together with Lenvima that is taken once daily without stopping at the approved standard doses. And the patients were recruited at several different sites, 15 sites across Europe as well as Asia. We can go to the next slide. So I've already said that, but we have a mature median follow-up. So at the median time of follow-up of 10.5 months from this study, the median time to progression is now almost 11 months with a response rate of 24% and the disease control rate of 81%. And what is very interesting is that the patient in this study has been staying much longer than what we expected, with three patients still ongoing in the study and one patient still in response after two years of treatment. So when we talked about this data at ESMO, they generated very positive response in the scientific community. And this also generated an increased interest in participating in the upcoming and planned phase 2 study. So with this median time of progression of 10.9 months, we can go to the next slide, which is substantially longer. It compares favorable with all other relevant data sets in second line HSE. And what you can see to the right on this slide is 13 second line studies where we can see a median time to progression around four months. And this is regardless if it is with Lemvima after an ion mono or with other kinase inhibitor or with immune therapy combinations. So we can go to the next one. So as already mentioned, we had this WebEx, which was giving you the context and where Dr. Sean showed data from his publication where he compared sorafenib and lenvatinib in a relatively large data set this is a real world study where he could show that lenvatinib was significantly better than sorafenib but what he also did was he took the lenvatinib data in monotherapy lenvatinib and compare the data with the Phase 1b to a FosTROX-Lenvima study, which he is an investigator in. And that is what we discussed at this WebEx. So we can go to the next slide. What he showed them was that regardless if we look at time to progression, if we look at response rate or disease control rate, as you can see here, the difference, the results with FosTrox plus Lemvima signaled superiority in the second line. And according to his clinical experience, the response rate of Lemvima alone is not higher than 10%. And the time to progression is usually somewhere around four months. Why a TPP of almost 11 months was very impressive. But in order to get this kind of efficacy, Dr. Sean also has presented safety data. from the FosTrox plus Linvima study, our study at Esmond GI in June, where he really focused on the safety tolerability profile. And biopsies taken earlier, we have shown this earlier from a patient treated with FosTrox, either as monotherapy or in combination with Linvima, shows that FosTrox selectively kills tumor cells in the liver while sparing the normal liver cells. So this is what we saw, right? But we need to also look in the clinic. Is this true also in the clinic? Can we look at parameters in the liver that could confirm this? And we did so. We confirmed in an analysis where liver enzymes and other laboratory data, in this case, albiscore, that these laboratory data determines the liver function and they were stable during the treatment period. And which means that we preserve the liver functions, which enables an opportunity for durable efficacy. One additional tolerability parameter, really important for staying on treatment long term, is that the impact of platelets and neutrophils that we have shown earlier, we expected to impact them somewhat, but we could see in the analysis that these values were stable during time, And here you can see a 10-month follow-up where we have added all the laboratory analysis. So despite measuring neutrophils and thrombocytes four times per treatment for all the patients during all treatment cycles, very few measurements showed a level of grade three or more. That is the only sort of measurements that you can see below the orange line here. And this again enables patients to stay on treatment long-term. And these data were presented at ESMO together with a mature efficacy data set that we talked about. And all of this data can be found on Medivh's website. So what else have we been doing? We were recently at the International Liver Cancer Association's annual meeting, ILCA, in Toronto in October. And we were there. also to understand the most recent development and potential for upcoming changes in the treatment landscape and to meet with global expert and as well as potential investigator in the planned phase 2b study and what was what we can say was that it was a huge interest in meeting us and discuss our data and understand more about the upcoming study What is also important to understand when it comes to second-line HCC, I already said that, but I need to repeat it again, was that there were no new data in second-line HCC confirming the high need of alternatives in this patient population. The main focus was sort of trying to find out if systemic treatment in addition to surgery in earlier states and to other local treatment as states in intermediate states. could be a viable option, but none of this is ready for implementation. So no change around earlier sort of stages of HEC patients that potentially could impact the development of FOSTRUX plus Lanvima. So the overall takeaway is that it is important to see new second-line treatment and that the development of FOSTROS plus Lenvima gains substantial interest and is considered, really considered as a new promising new option. So Jens already said that, and we are excited about the combination, but we have also published the clinical proof of concept with post-trux as monotherapy in Journal of Hepatocellular Carcinoma. And the results from this study show that post-trux was safe and tolerable with preliminary anti-tumor activity, and it confirmed the liver targeted and selective mechanism of action, as I already said, with the biopsies. So the next step is the randomized phase two study that is really designed with the appropriate statistical power to show efficacy benefit on overall response rate as the primary endpoint. And this is an endpoint that FDA accept for a potential accelerated approval. And the aim is also to use this study to file for breakthrough therapy designation and to initiate an accelerated approval process. And before I leave it to Jens, I think that this study, we really have the opportunity to truly make a meaningful impact for second-line liver cancer patients.

Thank you, Pia. And one critical element clearly, of course, in taking this program forward, sort of with a randomized phase 2b of this sort of size and magnitude is to ensure that we have sort of appropriate sort of clinical trial supply. So we were sort of very sort of happy to be able to announce on Monday that we've now signed the clinical trial collaboration and supply agreement with As part of that, they will then, of course, provide drug supply, which would otherwise be quite a significant investment needed to sort of support the full study, while we then, of course, still retain all the rights to the compound. What we will also do is that we will establish a joint development committee with ASI for the planning and execution of the study. And we are quite happy with ASI making this commitment with regards to, because this generates quite a bit of work on their behalf. with regards to sort of supporting the study as we now sort of embark into additional countries in Asia and including in the US where they have sort of experienced capabilities in the past. So we truly believe that the sort of having this sort of joint development with them would sort of further support doing the study in the best possible qualitative way but also be able to drive it with the highest possible speed. So I mean clearly we've had sort of discussions with ACI with regards to sort of this supply and for them to supply is not always sort of super obvious I mean they go into this kind of agreement if they think that the the kind of the study has an opportunity to deliver on the promise. So the fact that they are engaging both from a supply perspective and they are engaging from a timing perspective, so the further validates the potential of FosTrox plus Lenvima in addition to Lenvima and clearly they are the company that knows the best what Lendvima alone, what benefit that provides. So we're quite happy with the confirmation and the belief in the combination, what the combination can provide on top of Lendvima. So that means this is yet another step in our preparations for that randomized phase 2b. And those preparations are proceeding according to plan. And as we've communicated earlier, we're on track to open an IND in the US before end of year or in Q4. So things continue to move along quite nicely in the preparations. Just to kind of repeat a little bit in terms of one other element that we're seeing, Pia talked about the significant unmet medical need. We talk about the lack of treatment options in second line, whereas there's quite a bit of focus on first line. The other thing we see that is also coming for is that the unfortunately, there is the growth of liver cancer or the incidence growth of liver cancer is not slowing down. If anything, it's actually sort of increasing. So what we see is, and this is in the West and in the East, sort of a growth and a growth that is very much driven by the obesity. uh sort of pandemic and and the the fatty liver disease that that causes so uh what we foresee is clearly a commercial opportunity that is growing so when we look to 2030 that commercial opportunity in second line market alone again where there are no approved treatment options today will be valued in excess of 2.5 billion if our treatment duration if sort of if the the treat time to progression we're seeing in the current study with phosphorus and vima if that carries through when we assume a sort of a treatment option in line with that then the mark the value of that market actually increases further and starts to get close to sort of four billion so the second line liver cancer market alone is clearly of sort of a large potential. And then going forward, we can look to sort of move it up in earlier treatment lines, potentially liver metastases from other tumors. But if we just hone in on second line liver cancer, where there are no treatment options today, it is a sizable commercial opportunity. And the other part, I just want to kind of take a step back and reflect on, uh is that in oncology in general if you look across tumor types it's usually uh quite a competitive landscape but second line liver cancer is a bit different so if i if i take a bit of time to walk through this slide on the left hand side is the current treatment algorithm. And we've talked about this before. I think it's important to emphasize because it isn't changing and there's a window that we have an opportunity to move into. In first line today, all patients, I would argue, or almost all patients will receive an immunotherapy combination as a standard of care. Usually that's the centric Avastin. And that's the case since 2021. There is a number of studies ongoing to evaluate other immunotherapy combinations in first line. So there's a number of regimens competing to win in first line space. But patients who progress on an IO combination, they will move into second line and they will need something different. So re-challenging with an immunotherapy isn't a successful way forward. So they will need a different mechanism of action and different approach to killing cancer cells in the second line. And still, there are no approvals. There's no scientific evidence support what to use in second line. And the community is somewhat almost screaming for alternatives, because there is a lack of treatment options. So with the combination of FosF and Vima, again, there is an opportunity to move with speed and be the first approved option. Because when you look on the right-hand side of the slide, just kind of highlighting the competitive landscape, then Yes, as in the kind of the green field, there are a number of immunotherapies that are evaluated in second line, but we've already seen from ASCO that that doesn't work. And you can probably try a number of different immunotherapies and it will still show the same, that re-challenging doesn't work. So if you want to go down a new route with a novel combination with different mechanism of action, we are at the forefront and from the development perspective so again one of the reasons why we are trying to move with speed and one of the reasons why the external community and the kols are are pushing us to sort of get to phase 2b as quickly as we we possibly can so uh sort of with that I just kind of summarize things. Well, hang on a bit, move the slide. So in short, kind of summarize this in four different buckets. We are developing the first oral liver targeted treatment, and we've shown that we are able to deliver the drug locally in the liver. And when in the liver, we kill tumor cells and not healthy liver cells. That translates up to the right to quite substantially improved clinical benefit for patients in second line setting, including a 10.9 months time to progression. And the bottom left, there is an opportunity to move with speed in order to become that first approved treatment option. Hence our plan global phase to be in order to, and the bottom right, sort of get first to a market opportunity that is valued at sort of beyond 2.5 billion by the time sort of when we get there. And the other thing that's important is that there is also a, we've seen that in the current study, the willingness to recruit patients to the combination is strong, meaning at the time of an approval, the resistance to uptake commercially would be very, very low. So with that Magnus, we move to financials.