Medivir AB (publ)

Thank you very much and a warm welcome everyone to the quarter two results webcast here at Medivir. I hope everyone has had a great summer as we sort of kick off again after a warm and long summer vacation. Here at Medivir, we closed out quarter two sort of at the beginning of the summer on a very high note. when we presented sort of a strong data set for the FosTrux-Linvima combination at the ESMO GI Congress in Munich. And we will come back to that and share a bit more details today in terms of the data presented and how we're now working forward with the FosTrux development program. So, important information which you will find as you access the presentation on the website. As mentioned, In quarter two, we were able to share a very exciting data set at SMOGI, where we can see or could see for the phospho-structyl enzima combination a superior efficacy compared with what has been shown in previous published studies in the second-line liver cancer space. Equally important, we could confirm in that data set, and Fredrik will come back to that in a bit more detail, the liver targeted approach, i.e. the killing of cancer cells in the liver, without having a negative impact on normal liver function. Highly important for the treatment of liver cancer. And in addition, we are seeing the sort of important or improved efficacy we are also accelerating the post-trust development according to plan. In the room with me, I have, of course, our CFO, Magnus Kristensen, who will sort of come back to the financial details at the end. And I'm also in the room with CMO Pia Baumann, who will go through the clinical data from SWGI and will be accompanied by our CSO, Fredrik Örberg. So as mentioned, sort of the full focus here at Medivir is the continued acceleration of post-trust development. We've shared data previously, but that data set was sort of highly strengthened by the median time to progression that we showed at SMU-GEI of 10.8 months. And before we go into the details, just to sort of take a slightly step back, One of the things that we are seeing, and liver cancer is not the most common tumor type today, but it is a tumor type that is growing quite rapidly. It's the fastest growing tumor type in the US, driven many times by the obesity pandemic we are seeing, which is contributing to a strong increase in fatty liver disease. which also contributes quite strongly to patients or people being diagnosed with advanced liver cancer. And as we have shared previously, we are now in the middle of running our global phase 1b two-way study, which we are running across three different countries and 15 sites. And we are sort of closing in on the end of the study. We shared an updated data set at ESMO GI, and we very much look forward to sharing additional details of the study and more detailed, more mature data set at the ESMO conference in Barcelona in a couple of weeks or actually three, four weeks. And before I then hand over to Pia to go through the clinical data that we presented a couple of months back, today is an exciting day. It's an important day. Today marks the on the day, the two year anniversary of the longest running or the longest treated patient in the study. And it's a patient that is still on treatment and is still responding to treatment. So highly, highly encouraging from an ability to stay on treatment long-term and most importantly to benefit long-term from treatment. So with that, I hand over to Pia to go through more of the details in terms of what we shared. a few months back.

So, yeah, the latest presentation at SMO GI, we had data from, as Jens said, from the phase 1b-2a study with FosDrux plus Lemvima, and it was in 21 patients who had progressed on mainly an immunotherapy combination. As you can see, just to remind you a little bit about what are the patients in this study and what disease characteristics do they have. And that means that 70% of these patients actually had been treated locally as well with TACE primarily, but also others or local therapies. And 70% about had metastasis also outside the liver. And this is important for the combination. Phosphorus is really liver-targeted. But we are combining with what we think is the best available second-line treatment, lenvatinib, to ensure that also the metastasis outside the liver is treated. So I will actually hand over to Fredrik to go through a couple of details that was in this poster at ESMO-GI focused on the tumor selectivity and the data from ESMO. the biopsies that was done. So Fredrik, please go ahead.

Thank you. So you all know that one of the key objectives when developing a cancer therapy is selectivity. You really want to kill tumor cells without affecting negatively normal cells in the body. And we have in the molecule, FosTrox, incorporated several features that achieved this and you will remember that we built this molecule on experience of delivering drugs to the liver inhibiting hepatitis c virus so the product contains features that gives the molecule a liver directed activity so stable in the gi tract Stable in blood, but rapidly metabolized in the liver. So that's one aspect. High exposure in the liver, low exposure systemically that would harm the patient. This we have demonstrated in preclinical models that we can achieve a really significant increase in liver exposure over normal delivery of chemotherapy. The other feature is, of course, that these patients, as Pia will come on to, they have a poor liver function. And we really do not want to affect the liver negatively. So other features of the molecule is that the orange part here is designed to inhibit DNA replication but not other aspects of cellular function, and thereby sparing normal hepatocytes. So these features we designed into the molecule, and if we move to the next slide, we're really happy to see that this pans out in the clinical study. So patients in cycle two, in combination study with levatinib, did have biopsies. And these biopsies were analyzed. And in this panel on the left, you will see both pre-dose archival tissue biopsies and biopsy on treatment. And what I can draw your attention to is the increase in DNA damage. So that's a feature that we normally don't see in the tumor unless they are treated, the patients, and it signifies DNA damage induced by Phosphorox. Also, we see hypoxia indicated by glucose transporter increase expression. And this is a feature of Lembatinib. So Lembatinib inhibits angiogenesis, induces lack of oxygen hypoxia in the tumor. And this hypoxia actually can synergize with the mechanism of action of FosTrox. So on the right hand panel is the summary of the data regarding DNA damage. from the eight evaluable biopsies that we took. And we can see that there's a significant increase of DNA damage in tumor tissue. However, gratifyingly, we do not see DNA damage in the adjacent liver tissue, suggesting that we have a selective tumor effect, not only a selective liver-directed effect. So with that, I leave to Pia to continue with the clinical data.

Thank you, Fredrik. I mean, it's really, really important what you talked about, this synergistic action with lenvatinib as well. And that becomes then even more important that FosTrox is selective in the liver because otherwise you might enhance also the toxicity in the liver. And as Fredrik already said, we have a patient population with a poor liver function. why tumor cell activity is really paramount when treating the liver with the liver tumor. So we don't want to impair the liver function further. So to confirm the results from the biopsy that Fredrik just talked about, we could see that what you see here on the slide is longitudinal liver enzyme data, ALT and AST. It's to the left. And this was over eight cycles. which we could see was stable without showing any deterioration, supporting the selectivity that we saw in the biopsies with FOX drugs, and also supporting that we didn't have sort of any negative effect on the combination with lenotinib. Something else that you often look at when you're looking at liver cancer patients is ALBI score, and that is assessed to sort of look at liver function, it's albumin plus bilirubin. And this analysis that we have from our data show that ALBI score, as you see to the right here, was stable with no change in the score. And that further supports this selectivity and also the tolerability which is a prerequisite for efficacy and in order to stay on the treatment to have a longer-term benefit. We can go to the next slide. So at earlier presentation, we have shown encouraging efficacy data. I'm sure that you have seen this already with an overall response rate of 24% and the disease control rate of 81%. In this population, again, it is a poor prognosis population. It is particularly important also to show how long they can benefit from the treatment, and that you can do with time to progression endpoint. And at ESMO GI, the estimated median time to progression was 10.8 months, which is very long in this patient population. And at that time point, five patients were still remaining on the study. And also at this time where we are right now in the study, data has matured enough to use the standard Kaplan-Meier approach with the median TTP. And this is an estimate about what the time to progression is most likely to be at the time of final read of the study. So this is what we normally use. We have presented before like an actual time point, which is not sort of the standard way of doing it, but that has been due to the fact that the data has not been mature enough. We can go to the next slide. So to put this median time to progression of 10.8 months seen in this phase 1b2a study into context, We are comparing with Lenvima and other second line treatments in HSE. And when we do that, it becomes clear that 10.8 months is quite a bit longer than the around four months in median TTP or PFS that is seen in studies that we have listed here to the right. This is not a comprehensive list, but as you remember, we have talked about before, this is like a zone or a data desert where we don't have much data. So with the LENVIMA data in second line after immunotherapy, it's mainly retrospective data. And what we can see there, this is the first part of the list, is that we have a TTP or PFS around two to six months. And this is really similar to what is seen with other TKIs in the second line HEC. And at the bottom of this list, So this is the data that was recently presented at ASCO, and it showed a disappointing PFS of only 2.8 months. And what was used here was an IO combination, in this case Pembro and Rigorafenib in second line, after using an IO combination in the first line setting. And this really supports the need for switching to another mechanism of action than what you actually used in the first time setting. So Janice has already talked a little bit about this but we are excited we are going to present data again and the impact of the data from SMODI was discussed with Dr. Sean at SMODI and that interview is available for you have not looked at it yet is available on Medivir's website And now, ESMOAR in Barcelona is really around the corner, and we will present data on the 16th of September from this phase 1b2a study with FosTrox blood lamina. And there we will present mature safety, because the primary endpoint was safety, and again, it's a prerequisite for efficacy. And we also now have mature efficacy results. uh these data will then later during the same day be shared and discussed in a webcast with dr sean and myself and we will provide more information shortly so what we can go to the next slide so what is the next step here and um based on the encouraging data that you have seen from the phase one b2a We are continuing the planning and the preparation for the randomized phase 2B study with FosTrox in combination with Lenvima versus Lenvima alone. And this is in second line, advanced HEC, that all of them have received a prior immunotherapy combination in first line. The first part of this study, as you can see here on the slide, will be a dose optimization run-in. And the second part will continue with the selected dose, also randomization, as you can see here. And the recruitment in this trial will take place in Europe, Asia, and in the US. And with our selected CRO, the feasibility is currently ongoing. And with that, I will leave it to Jens.

yeah just to kind of pick up on on where pia left off as i mean this is a picture you have seen previously that we have updated along the way just to sort of highlight that we continue to plow ahead not sure if that's a good expression but plow ahead with regards to preparing for the next phase and the activities that we had said that we were going to do that we continue to do So the update here, the things to note are the green boxes in the sense that the study feasibility is well underway and progressing nicely. And similarly, with regards to working with steering committee, selecting a PI and finalizing the protocol in order to open an IND in the US and in order to apply for national approvals in the different countries. Again, progressing very nicely. And as we've said before, we want to sort of share the data set as it matures, sort of regularly as it continues to, or at least that it has continued to improve. And as we communicated earlier, we have acceptance to present at ESMO, which we are super happy about because clearly that is the biggest and the most important ecology congress in Europe. So it's a good place to be with regards to generating sort of attention for a good data set and within a patient population where there is an urgent need for additional and for effective treatment alternatives. Again, we continue to sort of move ahead and with good pace with regards to preparing for the next phase. So with that, just to kind of some repetition, as we talked about before, just to kind of remind everyone that sort of whereas sometimes the liver cancer or the sort of liver cancer as a disease can sometimes be They're considered a relatively sort of small market, but the second land market in and of itself is actually valued at over two and a half billion dollars by 2030. And most importantly, it continues to grow. And the growth numbers are probably, if anything, underestimated. on the back of the the very sort of significant increase in sort of nash driven fatty liver disease driven and liver cancer we see across not just sort of western countries but also eastern countries and most importantly uh perhaps from a commercial opportunity perspective to keep in mind there are no approved treatment options in the second line setting today after the I-O combination. Almost all of the current studies ongoing, exploring, evaluating treatment alternatives are taking place in the first line setting. So the competition in second line is scarce. Most of the studies in the second line setting, they use and switch to another I-O And as you remember, a couple of minutes ago, Pia commented on the ASCO dataset for Keytruda plus Regorafenib, where they evaluated switching to another IO in second line, which showed the same as we have seen in other tumor types. Switching to another IO after a first-line IO is rarely an encouraging, you rarely get encouraging clinical results. With that, before I hand over to Magnus, in summary, we have shown today, and it's great to see that in the clinic as well, that the design of the drug is coming through in practical clinical terms as well, i.e. we have a unique and targeted mechanism that selectively kills cancer cells in the liver. That contributes to a strengthening of the data set and that have a super strong benefit of 10.8 months until tumor progression in the second line setting. And in a market where we do have a very clear opportunity to be first to market, a market worth over $2.5 billion on an annual basis. So with that, I hand over to Magnus.

Thank you, Jan. I could go to... Slide 20, please. We can see the financial summary for Q2 and year-to-date June. And I will only briefly comment on the Q2 results. And all numbers are in million six. To start off, from a financial viewpoint, Q2 was in line with our plan and with no real surprises, which is always good. And the turnover for quarter two amounts to around one million, and it relates to royalty income from StairClear. Other external expenses are higher compared to last year in the quarter and relates to the cost for the ongoing combination study, as well as seems the cost for the next phase of FOSDROX. Personal costs are a little higher and relate foremost to the shared savings program that was implemented in the quarter two. operating loss for Q2 is minus 37 which is higher than last year in the quarter and relates to what I said the clinical and CMC costs. The cash flow from the operating activities in Q2 amounts around 26 million minus which is in line with the plan that we have for the year. And the cash position at the end of Q2 is around 127 And according to the current assumption and according to the current plan that we have today, the cash run rate is into the end of Q1 2025. And with this, I will come back over to Jens.

Jens Nielsen Yeah. And sort of summary again, before we go to Q&A, we have a unique and targeted mechanism We're showing a benefit duration that hasn't been seen before in a very difficult to treat patient population with the opportunity to be first to market in a significantly sort of a high value market that the second line HCC space is. So with that, we stop our presentation and we go 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 Romanious from Red Eye. Please go ahead.

Hello, good afternoon. So I was thinking we could start where we left off about the funding situation. So I was wondering since you have around 130 million left and you guide that to last until the end of Q1, what are the cost activities that you have to do in the next three quarters since this implies costs will increase compared to Q2 and Q1.

Hi, Richard. Thank you for your question. And I really understand it if you do the calculation of the money in the cash flow operating outgoing in the Q2. And the easy answer is that, I mean, the cost that are not evenly distributed during the months and the quarters. And we have, like we said, we have some CMC investments that we are making now for the next phase, for the phase 2b. But of course we follow this very carefully and we will update if we will have any changes and then update of course. We look at each quarter and But I can say that we will have a positive cash flow in the Q1 according to the current assumptions today. I hope that answers your question, Richard.

Okay. I interpret that as meaning this is, let's say, a conservative estimate.

It's more conservative than a positive viewpoint, yes.

Okay. And then a question for Jens. about obviously the most I think critical thing you need to do now is find a partner so could you tell me but more how more about that that process how it's going what more data do you think a partner wants to see or do you have all the data that's needed or other preparations I mean I would say the following I mean it

I mean, the partner discussions and the question regarding maturity of data will always be a fluid process, of course. I mean, there will never be a sort of a set point in time when, okay, now it's not a binary sort of switch on and off. But I guess clearly from our perspective, we have seen throughout the year, sort of from when we started at ASCO GI, that sort of The data has sort of strengthened. Patients have stayed on treatment longer. That has to some extent delayed the maturity of the study and the closing of the study. But the positive thing is that data has strengthened. And in any partner discussions, you, of course, want to utilize sort of as mature, as strong data as you possibly can. But I think what we're alluding to now and I think we commented on kind of mentioned in the in the in the quarter two results sort of in my introduction that we are looking forward to presenting more detailed and mature data sort of from a safety perspective definitely but also from a clinical sort of from an efficacy perspective at ESMO in Barcelona so So with that, we are saying that we're now getting to a point where the data we see now from an efficacy and safety point of view is sort of close to, it's not going to be a final readout, but it's close to sort of a final outcome. And that means that there's not much more from a data perspective that with regards to partnering discussions, i.e. moving to a situation where We have what we have, and now it's time to close out any partnering discussions. We have had and we continue to have discussions, but with regards to specific details, etc., I think we've said all along that we will share information when we have news to share, when we have something to confirm.

That makes sense. I guess that's one reason you raised money earlier this year to wait for data to mature. Another timeline question. When do you think you will be ready to submit the MDA and when do you think the base two can start?

I think we've I'll use the word conservative before. What we have said is that we are looking to file for the IND in the second half of the year. That is a conservative estimate, in the sense that it's not going to come towards the back end of the year. But I think the important part is that That process, together with feasibility and other things, are progressing according to plan. I think I've said previously that we've frantically been moving to, would it be possible to initiate the study this year? that i i've concluded before that that's going to be a challenge but sort of we look to sort of the the plan is to initiate the study in the i mean in in the beginning of the first half of 2025 but sort of from an ind perspective without giving away a specific date and it's progressing well and together with other preparatory activities

Okay, another thing came to my mind that would be interesting to hear your thoughts on, maybe I've asked this question before, but it's worth repeating in any case. Are the patient characteristics in this osteoclastal environment studied Does that represent a typical liver cancer patient or the battery worse condition?

So there are a couple of exclusion criteria. It depends on what trial you are looking at. And again, in this patient population, the trials are scarce. So now I'm talking mainly about the first-line population. Where you exclude patients that, for example, have Now I'm going to a little bit of a detail, but they have a narrow macrovascular invasion in vena cava, for example. We haven't excluded these patients because this is an old common population. We also have, and now I'm talking about second line, we say that we are in second line, right, but we also have third line patients. So we didn't have that strict exclusion criteria in our study, which means that we have more like an old common population, but they are very much sort of align with what a second line HSE patients would look like. If you're not in a clinical trial, that's what I mean, like in the clinical setting.

Great. That's all for me. Thank you.

As a reminder, if you wish to ask a question, please dial pound key 5 on your telephone keypad. There are no more questions at this time, so I hand the conference back to the speakers for any closing comments.

And what I will do then, just kind of move the slide forward. I'll repeat sort of what I've said previously to kind of end on that note in the sense that we have a unique drug on our hand from a mechanistic point of view designed to treat liver cancer. It is treating liver cancer in a quite effective way, in a way that we haven't sort of seen in the second line space before. and the combination is quite tolerable together with Linvima, very encouraging. And we continue to prepare for the next phase. We're moving forward with as much speed as we possibly can because there is a window and there is a window of opportunity to be the first approved treatment alternative in the patient population where there is an extremely high unmet medical need, a population that is growing quite fast. So with that, we are highly encouraged by the end of Q2. And now we shift gears towards the next couple of weeks. And we look forward to sharing additional updates and running a webcast with a bit more details regarding that study data as well, together with one of our key investigators in the study from the ESMO Congress in Barcelona on September 16. So with that, thank you everyone for dialing in and have a good rest of the day.