Welcome to Medivir Q2 report 2022. Throughout the call, all participants will be in listen-only mode, and afterwards, there will be a question and answer session. If you wish to ask a question, please press zero one on your telephone keypad. Today, I'm pleased to present CEO Jens Lindberg and CFO Magnus Christensen and CSO Fredrik Öberg. Please begin your meeting. Thank you, operator. We can immediately move to slide two just for some further sort of color on who we are. On the call myself, and I am the CEO since January this year. Then Magnus, our CFO, and Fredrik, our CSO, will be sharing the presentations and will be sort of sharing the Q&A session at the end of the call as well. With that, we can move to slide three, please. Important slide. Please access the slides on our website, and you can read it there in a bit more detail, and we'll jump forward. We can jump ahead to slide number five, please, operator. In terms of highlights during last quarter, we'll divide things into sort of two categories. One focused on our lead asset, Fostrox, and the other with regards to the other portfolio development. Fostrox for liver cancer is our lead asset and where we focus our efforts. During the last quarter, we are now up and running across our different sort of study sites in U.K., Spain, and South Korea. There's been a lot of focus on getting and activating sites, getting them up and running. Now that we have it up and running, we're also looking to add additional sites and investigators, especially in Korea, where we see a good movement. As we communicated in our report, we did see during the last quarter a slower than planned study recruitment rate in the European countries. We have launched a set of initiatives to overcome that. We've set up conditions that will increase the recruitment rate during the second half of 2022. We've seen also sort of good movements over summer. We'll touch on that in a little bit, sort of slightly later. Perhaps not the biggest news. We've had our INN name approved previously, and now we also have it approved as a drug name by USAN. Good to have the same drug name approved. The final element with regards to Fostrox and liver cancer is that we may be a bit weird to put a negative outcome of another study as a highlight, but I think that we have seen a press release from Merck and Eisai where they communicated that the LEAP-02 study read out negatively, and we'll touch a little bit more on that. The important element for us is that it further highlights the need for alternative combination therapies with different mechanisms of action in the HCC space. With regards to our other portfolio, a couple of movements or progressions during the quarter. The Birinapant compound that we have outlicensed to IGM Biosciences, they continue to study the combination with their own IGM-8444 in solid tumors, and they have communicated that they've cleared the third of four planned dose escalation cohorts with no DLTs. The other element is that a previously outlicensed program, MBLI program or Metallo Beta-Lactamase inhibitor, which was outlicensed to a company called AMR Centre, which is today named InfeX Therapeutics. They have presented additional preclinical data in 2022 and also communicated that they are moving the program into phase I, sort of 2022, 2023 timeframe. We'll touch a little bit more on that as well. If we move forward one slide, go to slide six. This is just our pipeline overview. The only thing to sort of mention here is that sort of for those of you who've seen it before, we have added back sort of the MBLI program now that it has progressed and moved, and we're seeing sort of movement towards clinic. We added it in, so it's here as well. From a financial viewpoint, there's a revenue share potential. Whenever InfeX would sort of further sort of partner with someone or outlicense or sell it, then any revenue as part of that agreement will be shared with us. Let's start with our lead program fostroxacitabine bralpamide. We can go to slide eight, please. As mentioned, we have seen a slightly slower than planned recruitment rate in our European centers. That's been analyzed, and we've looked at what can we do to overcome that and speed things up. We have sort of taken on initiatives in three buckets. One, we have amended the protocol, where we have simplified the inclusion criteria somewhat. Most importantly, we have broadened the criteria. Now we sort of allow for inclusion of second line as well as third line patients. Third line patients who aren't too sort of sick in their liver disease, but sort of third line patients are now eligible as well, to be included. We have also, we're also sort of adding additional investigators and sites in existing countries, primarily focused on Korea, where we see sort of further potential to further drive recruitment rate up. We're also exploring additional countries to go into, and looking at feasibilities across a few countries. When we have honed in on selection, we'll communicate a bit sort of further detail. The third part, we are seeing sort of increased competition, sort of more studies have started in the wake of COVID-19. In order to ensure engagement, et cetera, we have sort of further increased our presence and our activity at the activated trial sites to engage sites to continue to recruit to the study. As I mentioned previously, sort of these are initiatives that we, to some extent, have launched, and we're seeing sort of positive movement. There are sort of further benefits to come from this. For example, the protocol amendment, they have just this week been approved in both Korea and in the U.K. That will further fuel sort of uptake in recruitment speed. Looking so good with regards to sort of creating a change in that respect and so we feel positive about the future. With regards to other elements, we can go if you move to slide nine. I did comment a bit on the LEAP-02 study. For those of you who may not be as familiar with the study, it is a first-line study in unresectable HCC, which is comparing PD-1 Keytruda plus TKI Lenvima, comparing it with Lenvima monotherapy treatment to progressive disease, and they've had a study with dual primary endpoints. A couple of things to note here. They've just announced that it did not meet its dual primary endpoint in OS and PFS. Since they've only shared a press release so far, it's too early to speculate on the reasons for the negative outcome, and we need to see the data in more detail to sort of further analyze. That data will be presented at an upcoming medical conference. We don't know yet, but there is a sort of high likelihood that it will be presented at ESMO in Paris in a couple of weeks. Reason for mentioning it here is that sort of the HCC space is an evolving space, and it's clear that sort of these patients are difficult to treat. In order to get as best possible patient benefit, sort of combination therapies will be needed. What the LEAP-02 study is highlighting is that there will be a need for alternative combinations with compounds that have a different mechanism of action and come from a different class of drugs than the ones that are either used or in development today across HCC. This is where we believe that there is a great opportunity for Fostrox. I will stop there and I will hand over to Fredrik, who can go through some of the rationale as to why we believe that we fit nicely into that space in terms of alternative combination therapies. Fredrik, and then operator, you can go to slide 10. Thank you, Jens. As you may know, the current HCC therapy space is heavily dominated by two classes of drugs. Either stimulating the immune system with so-called immune checkpoint inhibitors, either anti-PD-1 or anti-PD-L1, but also anti-CTLA-4, which are usually then combined with other either anti-PD-1 or anti-PD-L1 antibodies. That's one part of the space. The other one is inhibiting angiogenesis, blocking the blood supply to the tumor, either by antibodies such as Avastin, anti-VEGF, or by multikinase inhibitors. These classes of drugs have been combined as for instance, the Keytruda plus Lenvima that Jens just mentioned. This has been a dominating combination therapy. With that in mind, what does Fostrox bring to the table? If we move to slide 11, this very briefly describes what Fostrox is. It's a pro-drug of a nucleoside analog. It delivers an already activated nucleoside, a nucleotide, with a mechanism that allows it to generate high concentrations in the liver, while at the same time minimizing its systemic exposure. It's orally administered. It's rapidly converted in the liver to the active metabolite. This active metabolite induces DNA damage and cell death of the tumor cells. We have, in the phase I part of our study, studied monotherapy of Fostrox. We have shown both that by bioanalysis that we deliver Fostrox to the liver cells and the tumor cells, but we have also shown proof of concept in terms of generating DNA damage or inducing DNA damage specifically in tumor cells. With biopsies from patients show clearly that in tumor cells we induce DNA damage, whereas in surrounding normal liver tissue, we don't observe that. We have shown proof of concept with the monotherapy. As Jens pointed out, of course, in the space and with the difficulty in treating HCC, combinations are required. If we move to slide number 12, there's good rationales for why a combination of maybe Fostrox with either checkpoint inhibitors or multikinase inhibitors should work. We know that Fostrox induces DNA damage and tumor cell death, and thereby potentially leading to increased tumor antigen presentation and increased immune response. We have preclinical data supporting this. The other combination with tyrosine kinase inhibitors, for that there's also a very good scientific rationale, and that is that blocking the tumor angiogenesis or blood supply will lead to hypoxia, lack of oxygen. This in turn leads to upregulation of enzymes that generate the active metabolite, which means that the combination generates more active Fostrox in the tumor when there is lack of oxygen. We have data from patient biopsies showing that we do induce DNA damage in hypoxic areas from the phase I part of the study. These regions are usually quite hard to reach with drugs. We're sort of very satisfied that we know that we can induce DNA damage in these regions. There's a good rationale for actually having increased effect in combination with these multikinase inhibitors. If we move to slide 13, this describes the current phase that we're in. Combining Fostrox with either the TKI Lenvima or Fostrox with the checkpoint inhibitor, the anti-PD-1 antibody Keytruda. We're starting this now, and we are in the phase of escalating the dose right now. These are dose cohorts of three patients. The aim of this part is of course to examine safety and tolerability, whereas we don't think that there will be any interactions since the mechanisms of action and the toxicity profiles are very different for these. We do need to escalate the dose until we reach a dose where we can say that this is the recommended phase two dose. This is going on in parallel for both the combination with Lenvima and with Keytruda. Once we have completed those cohorts and reached a dose that we think is the maximum dose, and it will be the recommended phase II dose, we move into the second part, which is an expansion phase to generate more data on the correct dose, to also be able to see some signals of efficacy and also to build a better understanding of the safety and tolerability. And as Jens mentioned, we are doing this across the world really, both with sites in Europe, in the U.K. and Spain currently, and also in South Korea. With that, I will hand over to Jens to continue. We can stay on this slide for a couple seconds because one, I just sort of realized that considering the latest changes in Korea and U.K. with regards to protocol, this slide should say patient population second and third line advanced inoperable HCC. Just pointing out that error. The other element is that sort of as you also see from the patient population, which has turned out to be quite important, that patients who have progressed on sort of standard of care therapy, i.e., including Atezo-Bev patients are included, which is an important element as Atezo-Bev today has become sort of clearly the standard of care as a first line treatment. We've said sort of all along and that we continue to do, we will sort of in terms of communication with regards to where we are and how things are progressing, we said that we will communicate when we have selected sort of when we finalize that first sort of dose escalation and we've selected the phase II dose and with the decision to move into the expansion phase, that's when we will sort of communicate. It might be that sort of there are different timelines for either of the arms, but sort of that's when we are planning to sort of make further communication and can provide a bit more color as well on sort of what we've seen in the different dose cohorts. We can move to the next slide 14, which is a relatively busy slide. I just wanted to keep it here just to say that under 2022, we have said, and we continue to say that selecting sort of combo dose and decision to move into dose expansion, that ambition to do that in 2022, and that ambition remains the same in terms of next steps. Another element to highlight, we can move to slide 15, please. I think I mentioned previously that sort of we're seeing a changing HCC landscape to some extent, if nothing else highlighted by the LEAP-2 study. A couple of things to highlight there on the treatment algorithm. It used to be that systemic therapies like Atezo-Bev or Fostrox or other drugs were primarily used in that advanced stage C. What we're seeing here is that more and more patients in the intermediate stage, rather than be treated with TACE or chemoembolization, et cetera, rather than be treated that way, they are given sort of first-line systemic therapy. We heard quite clearly from KOLs as of late that that's a movement that is very consistent. More and more patients flow into the systemic therapy, i.e., more and more patients are receiving first line, which also has a downstream impact of more patients will then be eligible or able to receive systemic second line systemic therapy for two reasons. One, because more are receiving first line, but also three, with better and better treatment options in first line, patients will be sort of healthier coming out of that first line and will be eligible to a larger degree for second line, which also has a downstream impact on third line. Good news for patients in terms of better treatments allow patients to also receive multiple lines of treatment, i.e., growing that sort of initial target population in second and third line, which where we are are planning to enter. That's a bit of a movement in the HCC landscape. We can sort of round things off with slide 16. This we've said before, and we will continue to say that sort of we believe that Fostrox is a unique and first in class potential treatment for liver cancer. There's clearly unmet need, as if nothing else evidenced by LEAP-2. We do believe that sort of we are more complementing than replacing existing therapies. We bring a different mechanism and a unique sort of combination partner to the other classes. Being also sort of a liver-targeted drug, then hopefully we can bypass sort of resistance mechanisms that we've sort of chemotherapy has seen sort of in previous sort of exploratory research. The other thing that we do know is that sort of inducing DNA damage and cell death through a cytotoxic is one well established in cancer, but two, also has a strong potential for attractive combinations. We know from other tumor areas that sort of the combination of PD-1 plus chemo, for example, is a very, very good combination. We believe that with Fostrox, we're able to bring those types of combination to a tumor type, i.e., liver cancer, where that wasn't possible before. We'll stop there with regards to Fostrox at this stage. If you, operator, go to slide 18, then Fredrik will take us through the movements that we've seen in the last quarter. Okay. Thank you. It's worthwhile spending a few minutes on the progress of the birinapant program. As you know, it was outlicensed to IGM. Therefore, it also has an IGM number, IGM-9427, as well as birinapant. It studied in phase one in combination with their IGM molecule, IGM-8444, which is an agonist of the death receptor 5. And there's a very good scientific rationale for combining these, inducing cell death at the same time as removing the anti-apoptotic molecules in the cell. This study was initiated in 2021, but it was of course preceded by a lot of preclinical work by IGM. One of those studies is highlighted on the right-hand side, negative breast cancer model in which combinations of IGM-8444, the DR5 agonist with birinapant shows a very, very large synergy in eradicating the tumor. You'll find more examples on IGM's homepage, really spectacular synergies observed in the preclinical model. Now they're moving this rapidly through the early clinical phases. They have concluded the third of the four planned birinapant combination dose escalation cohorts. Importantly, this was cleared with no DLTs, but also in particular, no clinically significant liver toxicity. Which was historically has been an issue with IgG-mediated agonists of T-cell DR5. That's very encouraging. For us, this means that we're moving along. The agreement allows for development, regulatory, and eventually sales milestone payments, plus then royalties on the sales eventually. We're very happy with this collaboration with very professional and dedicated teams at IGM. That's clearly something we're very happy with. If we move to slide 19. Another program outlicensed in 2017 within the anti-infective space has made some interesting progress by InfeX. One resistance mechanism in this multi-resistant bacteria is beta-lactamases, which essentially degrade many of the used antibiotics. In this collaboration or this licensing, an inhibitor program for metallo beta-lactamases has been licensed. InfeX has progressed this, showing very nice data preclinically in sensitizing bacteria which are resistant to antibiotics. We know that in these type of diseases, these type of indications, there's really a very good translation of the efficacy from preclinical models into the clinic. As long as safety and tolerability is okay, efficacy is very translatable from these early models. I think that's really great and probably really great for all patients who are going to be exposed to multi-resistant bacteria. As Jens highlighted, there's a revenue share agreement. When InfeX earns money, we get to share that. Although the need for this type of drugs, new antibiotics or ways of making old antibiotics effective again, there's a critical need for this. It has been very challenging to develop or to find commercial models that really work. I'll leave that to Jens to comment on. Yeah. The interesting part is 'cause as Fredrik Öberg said, it's been sort of this has been an area where there's been almost a resistance to developing new compounds because of the difficulty of kind of commercializing them. What has made the InfeX team sort of excited and thus ourselves as well is that there has been some quite interesting recent developments in financing solutions for novel antibiotics. There is NICE in the UK have launched a sort of almost like a prescription Netflix model. If you also do a bit of googling on the PASTEUR Act in the U.S., there's quite a bit of movement towards finding financing solutions where the financing isn't tied to sales volume, but rather sort of a prescription or availability. Basically, you get paid for developing the compound whether it's used or not, because the hospital doesn't want to overuse it. Quite interesting financing solutions potentially around the corner on this topic. With that, and as I said, they've communicated an intention to move into clinic towards the end of this year or beginning of next year. With that financial highlights, and we can move to slide 21. Magnus? Thank you, Jens. Yes, please see slide number 21, where you can see the financial summary for the Q2 and accumulated for Q1 and Q2 this year, which I will briefly comment on. All numbers are in million SEK. The turnover for Q2 amounts to SEK 500,000, which relates to royalty income from Xerclear. Accumulated, the turnover amounts to 1 million SEK, which is lower compared to last year. Last year, we was included the upfront payment, for the billion upfront outlicense deal to IGM Biosciences that Fredrik just mentioned. Other external expenses are high compared to last year, both in the quarter and accumulated, and relates foremost to higher clinical costs for the ongoing Fostrox combination study. Personnel cost is higher as well, that's due to more FTEs than last year. The operating loss for Q2 is around - 22 and higher than last year, and also due to the higher clinical cost with the Fostrox combination study. The cash flow from operating activities for this quarter amounts to - 18, which is lower, and then compared to Q1. More or less in line with the plan that we have for the year. The cash position at the end of Q2 is SEK 163. According to current plan, the cash run rate is well into the next year. With this, I will hand back over to Jenp. Thank you. We'll round things off with, if you move to slide 22, quite a busy slide, so I'll not go through all of it. You can access the slides on our website as well. Fredrik talked about the movement we've seen on the bottom with regards to the birinapant, the InfeX, et cetera. The other sort of what I just want to emphasize from a Fostrox perspective, sort of as I said before, we're now up and running sort of across our study sites. We're seeing sort of really good recruitment, movement in Korea, and we want to sort of put fuel on the fire, which is also why we're then aiming and in the progress of adding additional sites and investigators in South Korea to fuel that recruitment rate even further. Where we mentioned sort of where we're seeing sort of slower than planned rates in Europe. We do have initiatives in place, including the protocol amendment that have just now gone into effect. We've seen also sort of signals already sort of over summer of progression with regards to recruitment rate, which with the protocol amendment, we are seeing sort of further signals. In terms of making sure that we then from a future perspective, as I mentioned, our ambition to select a combination or combination doses and make a decision on moving into phase IIA during 2022, that ambition sort of still remains. With that, I think we stop there. We can well move to slide 23, for the sake of the argument and open up for Q&A if there are any questions on the line. Thank you. If you wish to ask a question, please press zero one on your telephone keypad. If you wish to withdraw your question, you may do so by pressing zero two to cancel. Our first question comes from Joe Pantginis from H.C. Wainwright. Please go ahead. Your line is now open. Good morning and good afternoon, gentlemen. Thank you for taking the question. A couple if you don't mind. First, glad to hear that you're doing these enrollment initiatives. Beyond Korea, first wanted to ask, where else you might be seeing initial movement as a result of your efforts? I think that's sort of one of the things that we have seen. Can you hear me, Joe? I can. Thank you. Yeah, sorry. I wasn't sure whether I was muted or not. I think sort of primarily in the summer is always a difficult period, and especially sort of we have three countries where we do. We have U.K., Spain and Korea. Spain is more of a sort of summer challenge, where we are anticipating to see a bit more movement in September now with the change of the protocol amendment. Where we've seen primarily is that a really good sort of pace in Korea and also a bit of movement in the U.K. We're getting sort of quite good feedback on sort of adjusting the protocol to include third line patients because we've gotten feedback that sort of we've been a bit too strict in that sort of second line population because there are actually quite a few third line patients who are doing quite well, and they're quite sort of healthy, sort of if you want to call it that way, that they've been unnecessarily excluded. There we've seen sort of kind of patients who are eligible and potentially waiting to be included as we sort of adjust the protocol. Got it. Actually, that's a very good segue to the second part of my question. Regarding the third-line patients then, it doesn't sound like you might have sort of, I mean, how would we call it, a strict window, you know, to be able to get them a patient enrolled in time before they advance rapidly. No, I mean, sort of we're including third line patients and we have the same sort of, what's the word I'm looking for? Sort of all the other elements with regards to sort of how healthy they need to be and their liver disease, they all remain the same. They still need to be sort of reasonably healthy from a liver disease perspective in order to be included in that third line setting. No other sort of specific set of restrictions regarding to the third line population. We've had that discussion with the investigators and the safety review committee, and it was felt to be unnecessary basically in terms of the population that they are seeing. What we have done, and I think that could be worth noting, is that we do have in the protocol the possibility of restricting the third line patient population in terms of numbers, especially for the expansion phase in two A. We want to make sure that we don't have too big of a third line population for the reason that you are sort of a little bit alluding to. They might be sort of progressing too fast. We want to make sure that we have a good balance, and we've made sure that in the protocol we have the opportunity then to sort of restrict that third line population. For now, I think it's important to establish the combination dose with the focus on safety elements. I think we might be a bit more liberal in that sort of balance between second and third line. In the dose escalation cohort, which is actually quite normal in the dose escalation phase. Make sense? Got it. It does. Thank you. That's very helpful. Just lastly, I guess a logistical question if you're depending on what you're willing to share, maybe for Magnus too. What your next anticipated milestone payment might be from IGM and potential size? Magnus, you wanna take that one? Yes, I could. Thank you. Thank you for the question, Joe. As I think that Fredrik mentioned is that IGM is really in the driving seat of this clinical study. But as Fredrik said, they're recruiting patients now to the planned four cohorts in the dose escalation phase. Hopefully it will not be that long, but we don't know that. IGM is in the driving seat for that study. It's so far so good as we see it. Maybe it would just be like an enrollment-based milestone that would be the next trigger? The triggers could be the next phase. I would say the next phase it will be a trigger milestone in the development phase, and we don't know when that phase will come. No, of course. Of course. Okay. Thanks a lot, guys. Thank you. Our next question comes from Richard Ramanius from Redeye. Please go ahead. Your line is now open. Hi, guys. I also have some questions. Maybe we can continue on the same line as before with the third-line patients. I was just wondering what kind of treatments will third-line patients have had before? What first-line, what second-line will they have had? I think one of the things that we have seen, and I didn't touch on that before, but sort of one of the things that we have seen, which is also a little bit of a trigger, is that there's been a change in the HCC landscape, i.e. Atezo-Bev has come in as sort of clearly the standard of care. It's equally then we've seen that sort of there has been and still are patients who were not able to receive Atezo-Bev in that first-line setting. Maybe because sort of Atezo-Bev wasn't eligible when they started or due to reimbursement, etc. One of the things is that we've seen is that patient may have received a TKI mono in that first line setting, and then in order to ensure that they receive Atezo-Bev, they get Atezo-Bev in second line. That's a flow that we have seen that has been of interest to make sure that, well, just because they move that way, they're not excluded from being included in our study. Because those patients are many times can be quite sort of healthy, if you wanna call it that way, as they come out of that second line. Okay. It makes sense. You think all patients that will be part of your trial will have received the standard? I think it's quite likely that sort of patients they may not have gone sort of exactly that sort of stepwise route with sort of first maybe a single TKI and then Atezo-Bev in second line. With regards to, sort of, we do believe that sort of most patients who enter our study, they will have received the Atezo-Bev combination either as a first line or maybe as a second line. I think that seems relatively clear these days. Maybe there are pockets in the world where that combination isn't yet reimbursed and therefore, there might be a challenge. Most patients will have received the Atezo-Bev combination either in first or in second line. Okay. Yeah, yeah, that makes sense. Yeah. I was thinking about to make comparisons logical about with benchmarks, if it might affect that if you have two different combinations of second line and third line, if you want to compare your results with a benchmark. I think that's something that we're gonna need to watch for. I think that's why I sort of. If I go back to my previous comment, we've been quite sort of in those discussions in terms of expanding into third line. There have been many or allowing third line patients to be included as well. Sort of that's why we've been quite conscious in the discussions with the investigators and looking ahead to make sure that we are able to sort of restrict that sort of third line percentage or cohort as we move into the expansion phase. I think at this stage when we're looking at safety, just establishing the combination dose, etcetera, then it's not as important to put it that way. It's more about sort of the safety, how are the combinations, how are they working, what doses is not kind of providing DLTs, etc. I think in this phase, less relevant or less important, if I wanna call it that way. Whereas in that expansion phase, yes, that is an element that could be of relevance. That's why we also put into the protocol, the ability to sort of restrict that population to ensure that we don't land with a challenge with regards to comparison. Okay. Yeah, yeah, that absolutely makes sense. I was thinking about but another thing concerning the design of this study. Will you distinguish between first line responders or non-responders and then who progress? Because I was thinking if a patient responds to checkpoint inhibitor then relapses, maybe they'll respond to another type of checkpoint inhibitor that might influence results. Yeah. That could be the case as well. But I think in terms of this, that's a bit difficult for us to. How should I put it? We sort of, since we are allowing sort of physicians to choose arm, i.e., sort of they sit with the decision as to whether a patient should go into the Lenvima arm or the pembrolizumab plus Fostrox arm, i.e., they will draw the, "Okay, what have the patient been on before?" Then they treat accordingly. I mean, what we have seen is that, it's not. How should I put this now? It's relatively logical to a patient that comes out of an Atezo-Bev combination. It's relatively logical to put that patient on Lenvima for sort of mechanistic reasons, et cetera. Similarly, if you come out of a TKI-based treatment, then it would be logical to put that patient on a sort of pembrolizumab Fostrox solution. That's a decision that lies with the investigator. Does that make sense? Yeah. Does that sort of answer your question? Yeah. Yeah. Yeah. Makes sense. I mean, as we go forward and we start to go into expansion phase, et cetera, then you get to a point where maybe you can start to explore, okay, well, are there different sort of patient types coming out of first line that might respond differently, et cetera? At this stage, the important thing is to establish a dose and then move to expansion phase just to make sure that we see the signals that are needed and then into B, then we can start to explore sort of those types of details, I would argue. Yeah. 'Cause under this phase IIB, is that the IND that you will submit in 2023? Is that the phase IIB trial? Yeah. The U.S. plans for an IND are there to not include U.S. sites in the current study, but to make sure that the U.S. sites are eligible to participate in the IIB. Yes. Will that not be a potentially pivotal trial, I guess. Well, sort of we are planning. We have to plan for success, and we are planning for an outcome where we see an overall response rate in that sort of IIA expansion phase that could potentially or signals that could potentially then warrant sort of a the IIB to be sort of a potential for accelerated approval study. In that IIB study, we would then sort of maybe sort of hopefully sort of show a sort of overall response rates in the IIB study that will be good enough for an accelerated approval in the U.S. or conditional approval in EU. That's our aim. I mean, it depends a little bit on how the world is moving. Again, going back to LEAP-2, we're not seeing a wealth of combinations or other data sets that are sort of making the unmet need lower, on the contrary sort of. If there's an opportunity to show, let's say, overall response rates of 25%, 30% in that second line space with a combo, that's quite an attractive ORR. And that ORR in a 2b study, unless something happens between now and then of significance, I would argue that that would enable a potential accelerated approval. That is still our aim. Yeah. It sounds like a good plan. Yeah. I guess that, yeah, that would probably be much smaller studies than the IMbrave150 first line that failed. If you could do it within groups with even higher unmet need in later lines. Yeah. I think we could. That we can speculate on, then we can clearly hope for it from an accelerated approval. Usually, those studies are a bit smaller, yes. But there's also, I think that in terms of study design and the size of study, is dependent on sort of assumptions you make regarding sort of what effect size will you see and power do you need. We will need to see a sort of, we need to see the IIA data before we draw any sort of conclusions on size of population in that. I don't know, Fredrik, if you have any further sort of you would like to add on that note. I think it's too early to say, would be my general comment. Anything else, Fredrik? Yes. No, that's clear that we need to see the IIA data in order to design the study properly. Of course, we're working with different scenarios. But that will need to be known before we put effort down in regards to size, for instance. Okay, perfect. Just one last quick question. I saw costs have come down quite drastically compared to Q1, specifically other external costs. So is that because of initial high costs to start clinics? Now that you started the clinics, the costs have come down. Magnus? Sounds like a question coming our way. Yes, I think so. Thank you, Richard. For the question, yes, that's correct. I mean, setting up the combination study, we had some initial costs, both for setting up the site, purchasing the Pembrolizumab and Lenvima and so on. Initially it was to starting up the study. That's correct. Okay, perfect. That was the question I had. Thanks for answering. Thank you, Richard. Thank you. Thank you. Our next question comes from Klas Palin from Erik Penser Bank. Please go ahead. Your line is now open. Yeah, thank you, and thanks for taking my questions. I would like to continue with this recruitment of patients and if you have been able to conclude if, I mean, the challenge in the IO seems to have, especially in Europe, is it due to the setting that you see, or is it competition from other clinical studies? As always, I think that we're all looking for that sort of what's the one silver bullet. Mm-hmm. I think that's one of the conclusions is that the silver bullet, it's not sort of one thing. Yes, we are seeing sort of in general, sort of an increased study competition post-COVID. There seems to be quite a few study starts sort of after the pandemic in general. Sort of a lot of. Mm-hmm. It's a bit sort of a narrow sector in some hospitals to some extent. There are competition in our space, Atezo-Bev being first line. Roche has the IMbrave251, which is the second population study where they are exploring the patients who have progressed on Atezo-Bev, and if they switch out Bev and add in Lenvima. That's a study they are running in a number of and quite a few centers. That's a sort of one study that is competing. It does vary a little bit. Mm-hmm. That's one element. The other element, just to be kind of clear on that, the third-line element in terms of allowing for third-line is not only driven by this, but there's also been a quite sort of clear, kind of. How should I put this now? Sort of, an expression from physicians that they are seeing that, sort of, they do have patients coming out of second-line these days that now are much more healthy and much more eligible for sort of serious systemic treatments that didn't use to be in the past. It seems like the patient population is also sort of slowly changing. There is a wish to be able to provide those also with combination treatments like this and don't exclude them necessarily. There is a patient element to it as well. Just sticking to this question, I just wonder when you're talking to your investigators, do they believe that it will be easier to add patients in third-line, or at least there is a lot of patients that could be added to the trial in the third-line, or might there be a lot of competition as well in the third-line setting? I did. I mean, sort of again, back to my previous comment, it's not. Mm. It is not 100% simple. I mean, there are studies in third line setting as well. Yes. I think sort of from a competition point of view, lower competition and yes, sort of clear the third line element, we hadn't made the change unless we sort of felt in the discussions with our investigators that, yeah, that will clearly. We will clearly be able to sort of recruit more patients or add in additional patients. Mm. To the study in this setting. That's also why sort of we also wanna make sure, sort of I'll come back to this one. We wanna make sure that there is a balance in the population as we go forward. Hence the need to put in the protocol for the expansion phase that we have the ability or opportunity to kind of restrict that third line so that the third line contributes now, but doesn't contribute too much as well. A balance there is needed. Okay, great. Just to reach a sort of a recommended phase II d ose. Yeah. In 2022, is that reachable or do you need to have a very strong uptake of new patients enrolled in the trial to reach that goal? No. As I said previously, our ambition, we've said it before and. Mm-hmm. We are saying it now, our ambition is to reach the end and make a decision on the recommended phase 2 dose in 2022. Sort of that ambition and plan. Yeah. Okay, great. has not changed. Perfect. My last question is about this InfeX deal, and you mentioned it's a revenue sharing deal. Is it possible to give any more details about how the deal is structured, or remind me at least? At the moment, no. I think that it'd be. We haven't really shared a lot in the past either. Clearly, it's a relatively sort of simple deal. There is a percentage that goes our way, depending on sort of how, sort of when in the phase that they do anything with it. The sooner they would sort of possibly sell it or do something with it, the higher percentage we get, and the more work they do, the lower percentage. But we haven't communicated any numbers on it. I think that, Magnus, maybe we could sort of have a little bit of think about in terms of sort of communicating some further details. Without having given that enough thought, Klas, let me kind of skip that answer or question. Yeah. Let us sort of provide maybe an appropriate response. There is basically a percentage that comes our way- Okay. Sort of for when they do something with it. They are not a commercialization company. Their intent is to develop it and then find someone else who brings it to market, either already in phase two or maybe later. They will be looking for someone to sort of outlicense the drug to take it forward. Okay, great. Thank you so much for your answers, and then have a great weekend. Thank you, Klas. Thank you. Our next question comes from Jonas Engblom. Please go ahead. The line is now open. Maybe it was Hans Engblom. I would guess it's Hans Engblom. Yes. Okay. I use, Hans, this is a bit dodgy now. Are you trying to get in with the wrong name? Yeah, yeah. Okay. Yeah. Okay. Anyway, hi, guys. I wanted you to be a little more specific, and I want to rephrase one of Joe's questions. Okay. When is the earliest date? I'm not asking about an answer or anything, but when is the earliest date you can receive a milestone from IGM according to the agreement? Magnus? Hi. You want to take that one? Thank you for your question. I mean, the next phase milestone potential is when they go into phase two. That's what I can say. Okay. Okay. Like, clearly then that depends on how quickly do they move into phase II, and that's a decision. I mean, we don't sit with that decision. We could speculate how quick can they be, but they also have other programs. That's why it's a bit, we're a bit uncomfortable. Sure. Yeah. Just to be sort of certain how we interpret that means that there is a possibility for a milestone in the middle of the present study that you find on ClinicalTrials.gov. Because that includes phase I and phase II. We will say that when they move into phase II, that triggers a milestone. Okay. Another question. You have sort of previously claimed that a reasonably large population can't use Tecentriq Avastin due to blood issues, et cetera. Now in your presentation today, it sounds like the combo Tecentriq Avastin is used very much despite your claim. Could you sort of put some more color into that? Yeah. Thank you for spotting that, Hans. Hoping that you wouldn't spot it. No, I'm kidding. This is actually a relatively simple one. The early signals and sort of some of the messaging that we have seen pointed to the bleeding risk, et cetera. We've done a bit of further work, and we're actually in the middle of a sort of deep dive on KOL interviews in the wake of LEAP-2, among other things. What's actually becoming quite clear, and Fredrik, you may wanna comment on this as well, but sort of we have been somewhat surprised, not. Well, okay, well, maybe that's right. We can conclude that the percentage of patients that they would be sort of afraid of using Atezo-Bev for bleeding risks seems to be a much lower percentage than we have seen kind of previous estimates of. I think it ranges from. I think the 40%, and maybe the 40% is the stretched number that sort of kind of comes out of the kind of AstraZeneca communication to some extent because of the HIMALAYA study and the durvalumab arm sort of positioning sort of well, there's a good chunk. Maybe that was a bit stretched, but it's interesting to see that sort of the latest interviews and the feedback we've gotten is that the percentage is way lower. I think that if I make a little bit of an average of the interviews we've had this week and last week, it points to maybe 10%. Okay. Ten percent is 10%, but then it's too small to even kind of really, really sort of make a fuss about. It seems to be that Atezo-Bev will be given to a clear majority of patients, and then the fear of that bleeding risk seems to be smaller than what we had initially sort of heard and estimated. That's a fair point. Okay. Just the last question. In terms of the sort of any new countries in Fostrox, is there sort of a priority on Europe or priority on Asia in your selection of another country? I think we are exploring both, but let's put it this way. We are seeing sort of we are sort of quite happy with sort of the movement and the recruitment in Korea and how the Korean sites are performing from a quality perspective and other things, which is why we're looking to add additional sites and investigators in Korea. I think from an Asian perspective then, that solves a need for further recruitment in Asia. With that respect, you could argue then that, well, maybe in terms of additional countries, perhaps Europe is of slightly bigger importance. We are exploring both, but I think that sort of, maybe then European countries would be a bit more, for that reason, to get the balance important in regards of additional countries. Below what you had in phase IA or phase IB mono would probably be likely, I guess, or something like that. Now you are speculating, Hans. Yep. I will refrain from sort of acknowledging your speculations. Okay. I'll say the following. I wouldn't necessarily hone in on Belgium for that reason. I think that what we want, what we need to do, which we are doing, we always need to do proper feasibility and look at countries and then whether Belgium then comes out good, then super good. If there's another country that comes out better, it doesn't matter that they were part of the phase 1 mono. That's. Yeah, we'll leave that one be. Yeah. We'll look at the feasibility, and then I'll say it might be other countries that sort of maybe look more promising at this stage. Okay, okay. Yeah. Thank you very much. Thank you. Thank you. Our next question comes from Richard Ramanius, Redeye. Please go ahead. Your line's now open. Hi. I was thinking about your cash position, and I have had, let's say, two questions related to that. If I remember correctly, you said that it will last well into 2023, but considering your present burn rate, I mean, why shouldn't it last into 2024? Another question, how well-prepared are you, or sort of related question, how well-prepared are you for some slight delays? What kind of margin do you have in your cash position? Magnus, I will leave that to you. Thank you, Hans, and thank you, Richard. Yes, I mean, the burn rate in Q2 was much lower than in Q1. According to the assessment that we have today and the plan we have today is that the cash burn rate is well into year 2023, and that is not including any potential milestones in the birinapant study or any other upfront milestones for other assets. According to the current plan we have today, the cash burn is well into next year. I will not say first year, second half or next year. It all depends on different factors which we carefully follow continuously. Our assessment today is in the second half of next year, the cash burn rate. Now. Does that answer your question, Richard? Yeah, yeah, I guess it does. Maybe you could to the last question, if you could have some short comment about this failed Keytruda/Lenvima study. Do you think that simplifies the landscape, for you going forward? I think it's the first thing is whether it simplifies. I think it's a little bit difficult to say. We need to see the data in a bit more detail to understand what was the difference, the numerical difference, even though there was no statistical difference, and how will that be interpreted by authorities, et cetera. I think that it. I think we need to see that data a bit more. I think the two things I think we can conclude are more what I said before. It does highlight the need for alternative combinations because combinations are the name of the game, and maybe this doesn't generate a super enthusiasm for PD-1 TKI combo. Maybe that sort of generates a bit more attention for or excitement for sort of an alternative like Fostrox. I think that's one element. The other element is that, I mean, we've talked about it as a potential sort of life cycle movement later down the line, sort of why stop with combo? Why not look at a triple? Perhaps a triple of Keytruda, Lenvima, Fostrox is perhaps no longer sort of an option that might not be. It might not be an option later down the line. I think those are the two things we can possibly conclude. In terms of simplification and other elements, I think we need to see the data in a bit more detail and interpret it before we can say what it means. Sort of again, the feedback we've had from our KOLs over the past couple of weeks are signaling that sort of both, sort of our approaches in terms of examining combo with Lenvima and combo with Pembrolizumab are still as valid and relevant as they used to be. It doesn't change that with regards to our current plans. Okay. Yeah. Perfect. Thanks. Thank you. No further questions at this time. I hand over to you speakers for any closing remarks. We just move to slide 24 and just say the following. That sort of in terms of upcoming activities, next week we are presenting at the Erik Penser Day on August 24th. We will be presenting at the Pareto Securities conference on September 7th, and we will be participating in the H.C. Wainwright conference in September. Not face-to-face, but sort of virtual attendance at the H.C. Wainwright conference. Those are activities that are upcoming. With that, we will conclude. Thank you all for dialing in. We, as we've tried to convey, we continue to move our lead program forward, and as we mentioned, with the aim of establishing that sort of combination dose and recommended phase II dose by during 2022. We've seen interesting and nice progress on a couple of our outlicensed assets during the past quarter. With that, thank you all, and have a good rest of the day. Take care.