Welcome to Medivir Q1 Report 2024. For the first part of the conference call, the participants will be in listen-only mode. During the questions and answer session, participants are able to ask questions by dialing hash 5 on their telephone keypad. Now, I will hand the conference over to CEO, Jens Lindberg. Please go ahead.
Thank you very much, and welcome everyone to our quarter one results webcast. Slightly different timing today, 10:00 A.M. rather than afternoon. But we will still be speaking English as we will be recording it for our English-speaking friends who might be accessing the webcast later today. So we're doing early today due to the Stockholm Exchange having a half day. Moving forward, important information, which you will find when we put the presentation on our webcast on our website afterwards. As we move into the Q1 results presentation, continued great progress across the business. Three key areas, most encouragingly, as we have reported previously, the combination of Fostrox Lenvima in the ongoing study, the efficacy continues to strengthen.
And Pia will go through more details in terms of what we're seeing in the patient's ability to stay on and benefit from treatment longer than expected. Two, we continue the acceleration of the Fostrox development according to plan as we come out of a supportive type C meeting with the FDA. And again, Pia will provide a bit more context on this in the call. And thirdly, also progress in other parts of the business. We announced just a week ago that we've been granted the rare pediatric disease designation for MIV-711, which Fredrik will touch upon as we move forward, to give you a bit more detail what the disease is, and we'll talk a little bit about the plans moving forward. And then finally, some progress for another one of our out-licensed compounds, MIV-701.
On the call today, I will be joined by our Chief Medical Officer, Pia Baumann, and Chief Financial Officer, Magnus Christensen, and our CSO, Fredrik Öberg, as well, and we will all be part of the Q&A session at the end. With that, we move into the progress, encouraging progress and promising results for Fostrox, and I hand it over to Pia.
Thank you very much, Jens. And, yeah, we can stay on this slide a little bit. The accelerated development, and Jens has already touched upon this, is what we have seen in the ongoing Phase 1, b to a study. Study is really support with the improved latest data and an increase in time to progression, the TTP, to now seven months. We can go to the next slide. So, just as a reminder, what are we developing here? Fostrox is a type of smart chemo that is really targeting the tumor in the liver. It is a capsule that you are taking orally, and with the design of this capsule, it stays stable in the GI tract until it reaches the liver, where it's rapidly activated by the enzyme there.
With this approach, it's possible to target the tumor in the liver and limiting the effect elsewhere in the body. So what happens next is that Fostrox is incorporated in the DNA in dividing cells, and this is really important. When the dividing cells then divide, Fostrox it contributes to the killing of the cells. And since normal liver cells divides very seldom, Fostrox is selectively killing the faster-dividing tumor cells. We can go to the next slide. So, we are developing Fostrox in advanced liver cancer, which is one of the most difficult to treat cancer, where there is a high need for tolerable, this is important, and with that, effective treatments. And we have seen a recent development and advancement in the treatment of liver cancer with the introduction of immunotherapies, and that was as late as 2020.
But still, only a minority respond to this available therapies across the treatment line. So if you can see on this slide, in the first line, it is about 30% that respond for around 6, maybe 7 months in median. When you go to the second-line treatment, when they have progressed on the first line, only 10% of the patients respond, and there is actually no approved treatments available after what is currently standard of care. And in this population, that's where we initially are targeting the development of Fostrox. You can go to the next slide. So now we are currently in a very exciting Phase with Fostrox in our ongoing Phase 1, B to A study. And we are, as said, evaluating Fostrox in liver cancer, and that is in combination with a kinase inhibitor, a TKI, named Lenvima in the second line.
This study is an open-label, single-arm study where we have included 21 patients. The study is fully recruited, and we have seen a couple of interim results, and they have been promising, and one of the key elements, of course, response rate and duration of response and all of that is important. But we can also see that the patients benefiting from this treatment and staying on the treatment is longer than we have actually anticipated originally. So we are going to have an upcoming congress presentation of this study, and that will be at ESMO GI in June, in Munich. And I will talk a little bit more with a couple of slides that is coming up about the latest data that continues to be encouraging, and we have seen efficacy improving, and the tolerability remains good.
So we can go to the next slide. So looking at the number of patients that has responded on the treatment, we are seeing a higher response rate than what has been reported in the second line previously. Remember, there is no approved treatment of the current standard of care. So we see about 24% in this study, and the expectation is around 10% with available treatments. In addition to this, and you can see that on this plot, hopefully, is that over 75% of the patients have a tumor that is shrinking, which is of great importance in liver cancer, where also those where you more or less can control the tumor, meaning that it stays stable, is considered as having a clinical benefit, and they can continue on the treatment.
Coming back to this, what is also important is how long the patients actually are able to stay on treatment with a clinical benefit. So we can go to the next slide. So, in this study, 7 patients are still on treatment in the study, where the one has been longest on the treatment is now exceeding 1.5 years, 1.5 year. The median time to progression has improved to 7 months, which is considerably longer than compared to the around 3.5 months that has been seen in the second line with available treatment alternatives. So very encouraging data. But we can go to the next slide. But, but efficacy is really dependent on that a new drug combination is safe and tolerable.
And with Fostrox added to Lenvima, the improved clinical benefit that I just showed you has not come with any new unexpected safety events. And the side effects that we have seen has mainly been temporary and hematological, that has been manageable, so that two out of three patients have been able to stay on the full dose of Fostrox without any dose modification. This is important, right? Because you want the patients to have as much efficacy as possible. Only one patient has discontinued Fostrox due to any side effects, and in addition, because we are combining with Lenvima, there have been no additional Lenvima-related adverse event, why the combination seems to be tolerable. So we can go to the next slide.
So with the promising data in this study, the current Phase 1b/2a study, together with a high unmet need in liver cancer, where nothing, I know I already said that, but this is really important, nothing is approved in this patient population that has progressed on first-line standard of care. We are continuing to accelerate the development of Fostrox, and in the planning of the next study that you can see here, which is a randomized Phase 2b, we are having continuous discussions and advice taking, with and from global clinical experts. And recently, as Jens already said, we had a meeting with the FDA. The feedback from the FDA resulted in an enhanced study design that you see here on this slide.
It has a similar size and the time estimate as the previous shown study design, and overall, FDA was supportive on the general design and agreed again that Lenvima is a rational combination partner and is the rational control arm in the randomized trial. So the change that you see here includes the addition of two Fostrox arms instead of one arm in a run-in Phase, and that will satisfy the need when we introduce, which we are, a new formulation of Fostrox, and that is for future commercial use. And this is, this dose to dose arm is also something that is recommended by the FDA in a project called Optimus, that FDA is driving to really optimize the dose that you are chosen.
The dose arm that is not selected, because there will be a selected in the 25 first patients that are randomized in three different arms. The dose arm that is not selected will be dropped before going into the main study, with around 100 patients in the active arm with Fostrox plus Lenvima and 50 patients in the control arm with placebo plus Lenvima... We have also changed the primary endpoint to ORR, which has been used for other accelerated approvals in the second line setting in liver cancer. This will later be confirmed in a study where overall survival will be included as the primary endpoint for the final approval. This is pretty much sort of where we are right now, and we are very encouraged by sort of going forward with this. With that, I'll leave it to Jens.
Thank you, Pia. So, kind of take-home message is what we have said before in terms of plans moving forward, and we have shown this slide before. So that plan stays the same, no change, apart from then sort of the two incorporated study design changes. So in terms of moving forward towards Phase IIb, we are well underway, preparing for the next study. I've highlighted in green here in the middle, a couple of the elements where we have seen sort of progress during Q1. One, as Pia outlined, we have had sort of FDA engagement to confirm that, yes, we are moving forward, with sort of kinda the same overall plan, and next step will be to sort of finalize study protocol and finalize things for submitting an IND.
The other elements also in the middle, we haven't talked so much about it, but in terms of making progress, in terms of moving forward with speed, selecting a CRO is an important element, and that has been progressing very nicely, and will also enable us to kind of start the study sort of in the early days of 2025. And we will communicate sort of selection of partner who will we work with, sort of as we finalize the agreement. And then also, we are as data are looking stronger and stronger, we are looking forward also, a congress presentation data update at one of the more important GI congresses, which is the ESMO GI Congress, towards the end of June. So again, continued progress in terms of our activities as we accelerate towards Phase IIb.
Pia touched on sort of the large unmet need, and it, it's sort of worthwhile sort of commenting upon that. Sort of we know that it's difficult to treat. It is the third leading cause of cancer death worldwide. It is increasing, and the increase of HCC is perhaps possibly underestimated, 'cause what we see is that on the back of the obesity pandemic and fatty liver disease, HCC is expected to increase quite drastically, and that is in the West, but also in the East, and there are no approved treatments in second-line post-IO combination, and there is relatively little development going on in that space. Most of the other companies are focusing on first-line treatment or earlier, leaving an open space for a new combination like Fostrox and Lenvima.
So the total market potential will be sort of above $2.5 billion as we get to 2030 and onwards, and with a significant chance that there for Fostrox to be the first approved treatment in this patient population. So to summarize things, Fostrox is a smart chemotherapy, selectively killing cancer cells in the liver. The outcomes that we are showing, and please remember that 30% of patients are still on treatment, but even with that, outcomes are improving. At current latest data cut, we are doubling the response rate, at least of what we've seen in previous second-line studies, and doubling of the time to progression.
Results that you would normally see in first line, we are now showing in second-line patients, and with a clear first-to-market opportunity of into a market worth $2.5 billion. So with that, we'll stop regards to Fostrox, and we will move into progress in other parts of the business that we have announced as of late. And the first one being sort of movement regarding MIV-711 granted rare pediatric disease designation in a pediatric disease we haven't talked about before, but I'll hand over to Fredrik to talk a little bit more about this.
Okay. Thank you, Jens. So, Legg-Calvé-Perthes disease, what, what is that? It's a hip disease affecting younger children, and there's currently no approved medicines to treat this, this disease. The incidence of this disease varies greatly, and but seems to somehow increase with latitude. So the further north you go, the higher the incidence. The highest risk in, in Caucasian population, is, is observed, and studies indicate that an incidence of around 9 per 100,000 children below 15 years of age is what you, you observe in, in the US. So it's, it's rare, but it's not insignificant. It usually occurs between 3 and 12 years of age, and the highest, incidence is around 5 to 7 years of age. There's a, there's a peak there.
So this is young children, and it's relatively rare, it's debilitating for the children, but what is not known is the actual cause of this disease. So while that is unclear despite lot of research efforts, the pathology or the process, the disease process is quite well understood. It all starts with a temporary disruption of blood supply to the femoral head. This in turn generates osteonecrosis or bone necrosis, and inflammation in the hip. And this then leads to, in itself and by mechanical stress, collapse and fragmentation of the femoral head. This then heals, but it doesn't heal well, and usually the outcome is a deformed femoral head. There's insufficient new bone formation and excessive bone degradation during this process.
There's no single gene that has been identified, and as I said, the actual cause is still unclear. But the outcome is then often a deformed femoral head, leading to, of course, pain and restrictions in movement during childhood, but also increased incidence of early osteoarthritis, for instance. So why are we excited about MIV-711 in this disease? There's a very strong scientific rationale for using a cathepsin K inhibitor in this disease. The necrosis and inflammation that this temporary lack of blood flow initiates increases the activity and the number of osteoclasts, and it also increases their expression of the bone-degrading enzyme, cathepsin K. This causes excessive bone degradation and contributes to the femoral head deformity.
So with a selective cathepsin K inhibitor, we could theoretically then reduce bone degradation, while also, and this is so, so important, maintaining the osteoclast, osteoblast coupling. So the osteoclast, while degrading bone, does also provide secreted signals and cell-cell interactions that stimulates the osteoblast to form bone, the anabolic cell. So remain or retaining this coupling, also means that we have the ability to stimulate bone formation, not only reduce the excessive bone degradation. And we know from Phase 2 studies in osteoarthritis, in clinical studies, that MIV-711 has demonstrated disease-modifying activity. So we're fairly sure that this activity is really true and there. We also then have support from animal data, from LCP, the animal models.
So in this model, we have demonstrated that MIV-711 can prevent femoral head deformity, improve bone structure, the trabecular structure. And this is also key to a medicine that is designed for children, of course, is that it does not negatively impact normal bone growth, as these children are not skeletally mature, and their bones grow during the disease period. So therefore, we're really excited that we have received this, the grant, the rare pediatric disease designation and orphan drug designation for MIV-711 in this disease, which really validates this concept. So with that, I will leave it to you, Jens.
Thank you. So in terms of then the question is, what does this then mean moving forward? And as we outlined briefly in the press release we shared the other week, we do see sort of partnership sort of collaboration approach moving forward. We do believe that there are other companies that might be sort of more suited to driving this kind of development in a pediatric disease moving forward. But we have also consciously sort of been quiet on that front up until now. We wanted to sort of file for the rare pediatric disease designation, because as Fredrik says, that is truly a validation from FDA that there is potential. They don't they don't grant an RPDD if there isn't evidence that this could provide benefit for the patient.
So we wanted to sort of have that validation from the FDA, and this now triggers sort of our outreach efforts to find a partner that can drive MIV-711 for this particular disease, moving forward. We haven't touched on it here, but there, there are other additional sort of pediatric disease opportunities where a cathepsin K inhibitor could also provide benefit. And what we will do is sort of similar to what we've done now with MIV-711 for LCPD. We will look to explore whether the potential is there as well. But with regards to LCPD, our aim is to establish a partnership and, for-- to drive that, have someone else drive that development forward in the fastest and best possible way... to then clearly realize the value of the compound.
So that's one element with regards to progress in the other area of the pipeline. And then as we have also communicated recently, these are a snapshot of our partnered programs, and I wanted to highlight is the one on the bottom, where we have seen recently positive Phase 1 data for another cathepsin K inhibitor, because MIV-701 is a cathepsin K inhibitor as well, which was in human use to begin with, but it turned out to be not suitable for humans, but very suitable for animal use, and it was out-licensed to VetBiolix, a French animal health company. They three things to comment on here.
One, they reported positive Phase one data from dogs with periodontal disease, and they also do have a Phase one study in cats ongoing, which they have a planned readout for later this year. A large size of this population, i.e., 80% of dogs and cats over three years of age, suffer from periodontal disease, and there are no disease-modifying treatments available or approved for this population. If you want to find more information and details about sort of this opportunity, VetBiolix, they have, they have a more meaty presentation available on their website, I believe.
But what they have also done is they have sort of outlined sort of estimated annual sales for the compound, if approved, and where they are quoting roughly $100 million annually by 2030 for MIV-701 in an oral care pet market that is actually estimated, size-wise, to $3 billion. So the commercial opportunity in animal health is also sort of significant. And as we communicated in our press release, this particular agreement is constructed in a way that the milestones, sort of the development and regulatory milestones, they are quite minor, whereas the value upside lies in the royalty rates that we would gain upon approval.
So that's where the real value lies from MIV- from a Medivir perspective. So with that said, we will move to the financial highlights. Magnus?
Thank you, Jens. Here you can see the financial summary for the quarter one, all numbers are million SEK, as usual. The turnover is in line with our forecast and amounts to SEK 0.5 million, which relates to royalty income for Xerclear. Other external expenses are higher compared to last year in the quarter, and relates foremost to the higher cost for the ongoing Fostrox plus Lenvima combination study. Personnel costs are higher and relate foremost to more employees compared to last year for the whole quarter. The operating loss for Q1 was -27 million SEK, which is in line with our forecast for this year.
The operating cash flow in the period is higher compared to last year and relates to a lower result, as well as most of the transaction costs related to the right issue in December last year, was paid in January this year, which I commented on in the Q4 webcast. Furthermore, the directed issue, approximately SEK 20 million, was received in January. The cash position at the end of Q1 is SEK 153 million, and is in line with our forecast. According to the current plan and with the current assumptions, the cash rate is into Q1 2025. With this, I will hand back over to Jens.
So thank you, Magnus. And as we have communicated today, we are on the one hand, super excited about the progress we've seen in other parts of the business, i.e., for our partnered programs and our other pipeline products, with regards to both MIV-711 and MIV-701 moving forward. But most importantly, we continue to be very encouraged with what we are seeing with Fostrox. There is a clear potential to improve second-line HCC therapy, become the first approved treatment option, as the first and the only targeted treatment, smart chemotherapy treatment for liver cancer.
As we have shown previously, and that has further strengthened today, the outcomes we're seeing in the study are quite impressive, with a doubling of response rate and a doubling of time to progression versus what has been seen before in second line, and what could be expected with sort of currently available second-line therapies. So we are accelerating the development and moving with speed, with the aim of becoming the first approved treatment in a market worth $2.5 billion. So with that, thank you everyone for listening in, and we move to the Q&A section.
If you wish to ask a question, please dial pound key five on your telephone keypad to enter the queue. If you wish to withdraw your question, please dial pound key six on your telephone keypad.... The next question comes from Richard Romanian from RedEye. Please go ahead.
Good morning. I have a few questions, mainly relates to fostrox, one about birinapant. Let's start with that one. What's the status of the collaboration with IGM Biosciences?
I can take that one, and we start with that one. The status for birinapant is as it was sort of last time, and as IGM communicated, I believe, towards the end of Q4 last year. For financial reasons, they have sort of halted a couple of their programs, and the impact on birinapant is as follows: They are combining it with their own compound, aplitabart, and then sort of they've run the dose escalation, no dose limiting toxicity. So all look good with regards to dose escalation. But they have come further in with aplitabart in combination in colorectal cancer.
So what they have communicated and decided to do is that they will be finalizing their expansion of aplitabart in colorectal cancer in combination with FOLFIRI, I believe. So they want to see a positive outcome of that before they push the button on moving forward with other aplitabart combinations, where then aplitabart and birinapant is one of those. So they want to sort of see proof of concept that aplitabart combination is working in colorectal cancer, which is the tumor type that has gone the furthest. And I believe that what they have communicated is that they are looking for a readout in 2024 for that combination before making sort of the final decision on how to move forward.
Perfect. That's useful. Then moving on to Fostrox. You've shown us the TTP figures for the Phase 2a trial. I was just wondering, would they differ anything materially from the PFS figures?
I think, Pia, that's a you question.
Yeah, so should I respond to that? Yeah, can you definitely do that?
Yes, yes, Pia. Please take the PFS question.
Yeah. So yeah, in liver cancer, it is not much, unfortunately for the patients, huge difference between PFS and time to progression. We haven't done the analysis because we are having an open label trial, so we can look at time to progression. With progression-free survival, we actually need to do another procedure to make sure that we are actually communicating the right thing, right. But it should not differ, considering what we have seen in other clinical trials in liver cancer, and particularly in the second line setting. I'm sure that everyone knows what the difference is. The time to progression is actually you look at the time they are on the study until they progress, and that is the event.
In progression-free survival, you also add death as an event, which means that if you have a long progression-free survival, for example, time to progression, PFS usually is different, because then some patients could have died of something else, considering they are a little bit older. But when you have a disease as liver cancer, they usually progress before they die, and that's why it's no difference.
Mm-hmm. So we've, I mean, Rica, one thing we've done sort of before communicating TTP, we've looked at sort of the difference between TTP and PFS across a whole range of, of studies in HCC, second line and first line, and the difference between the two measures are sort of on average, I, I sort of think 0.2 months. So they are basically the same across all the studies that we've, we've been able to evaluate in HCC.
Okay, good.
which is why we are quite comfortable sort of sharing and sort of being strong about sort of the efficacy we are seeing when we then reference TTP.
Yeah. No, that's sort of what I, what I am expected to have seen. I mean, the figures could change a lot more if patients survive much longer, as you said.
Yeah.
But yeah, that's great. Do you have any comments about the ORR versus PFS instead of PFS for the Phase 2 study? What do you think about that? Is that good, or would you prefer PFS?
Yeah, it has to do with... So why we ended up at PFS was because we had a lot of discussion with our external experts, global, as well as those like in the different countries, to understand sort of what is the most important endpoint for these patients. And as I said, when I presented the data, also stable disease. When you actually have an effect, you can control the tumor, is considered as clinical benefit. When you look at progression-free survival, that is what you measure. You measure all the patients that could stay on the treatment, that have clinical benefit, and you measure the time they have benefit. So for liver cancer, it is a very, very good endpoint. However, overall response rate is what is mainly used for accelerated approval....
The reason for that is that it takes shorter time to have that, endpoint as a readout, because usually the response is coming relatively early in the clinical trial, and it has been historically connected as a surrogate endpoint to overall survival. Overall survival is, always in liver cancer, the sort of final endpoint that you need to have included in your final trial. So, in order to have the best chance, I would say, to get an accelerated approval, overall response rate is probably what is going to be the best.
But with that, I must say, that the advice we got was that PFS is potentially better from a clinical perspective to really, really look at what is the difference between these different treatment that you have than progression-free survival or time to progression is a really, really good measure to see the difference between the different treatment.
Okay, that leads me to the last question, which is about the timeline for the Phase two study. So now you have those in part with two doses. How will that affect the timeline? When do you think the first patient will be recruited? I guess, sometime next year.
Well, yeah, we are, as Jens said, we are hoping to see the first patient in the beginning of 2025. When it comes to the timeline for the initiation of the study, that hasn't changed at all. Because we are dependent on the new formulation, as I mentioned, we need to sort of go for a formulation of Fostrox that could be commercially used, and that is what we are preparing for in the clinical trial. So that's why the change in when the study is starting has not changed because it's, again, dependent on this formulation.
The other timelines has not changed much either, due to the fact that the patients that are in the first part of the study, the 25 patients in the dose that will be selected, these 25 patients, together with the control arm, with Lenvima alone, they are going to be used in the second line. Well, in the second part, because we are sort of it looks like it's two parts, but in fact, it's only one part, which means that we are not going to have a, yeah, not very similar timelines is going to be appeared because there's no like... There's no real stop between the two different parts. It's just a continuous study, but you select the best dose arm and drop the other arm.
The other thing is that with an overall response rate that I said, that is, that we haven't shifted the primary endpoint, we will be able to look at the data a little bit quicker as well, because when you look at progression-free survival, you need to wait longer for your primary endpoint. So that's why it doesn't shift the timelines.
Okay, yeah, perfect. That's, that's, that's all for me. Thanks.
Thank you.
The next question comes from Clas Palén from Carnegie. Please go ahead.
Thank you for taking my questions. It will be the first one, at least, would be related to the updated study design and this, run-in Phase. This is like, 75 patients, if I'm correct-
Yes.
-that you are intending to re-recruit. At the end of this run-in Phase, will there be a sort of a go or no-go decision?
Yes, it will.
For the rest of the part?
Yeah, it will be a futility analysis done there. It's a dose selection, it's a safety for the new formulation, it's a dose selection.
Mm-hmm.
It will also be a futility analysis.
Okay, and this would be communicated publicly, I guess, of course, if you there would be a no-go decision, but also about the dosing and everything.
Yeah. So, so this is the thing, we need to keep the study, without any question about,
Mm-hmm
... compromising the integrity in the study. So we will have a data safety monitoring committee, which means that it's an independent committee from us, that will look at the data and do the recommendation. The reason for this is we will be able to use the patients in the first part and the second part for the analysis. Then we cannot, we can communicate, we will definitely be able to communicate if we can move further, and we don't reach any futility boundaries, but we will not be able to communicate any data at this time because it's like, it just continues. The study just continues.
Okay. When it comes to the OR, as a primary endpoint, I guess this would be measured by RECIST, not mRECIST?
So this is very interesting, actually, because we had a little bit of a discussion about that as well with the FDA when we had the opportunity. RECIST 1.1 is what is used, that is what has been validated, right? So we need to have that. But this is a Phase 2 study, so all the evidence of efficacy will contribute to what you have, the analysis of the study, if it is effective or not. Even if you have your primary endpoint as overall response rate with the RECIST 1.1, there will be secondary endpoint, which will look at the modified RECIST, where you actually are evaluating the viable or the living component of the tumor, which has proved or not proved. I can't say proved, right?
Because it's not validated, but it has shown in several studies that it's better correlated with, for example, overall survival. So it's, it's the totality of evidence that will be part of a potential accelerated approval.
Okay, great. Thank you. And when do you expect to have some interaction with the European authorities?
So we are planning to have that around our CMC. Obviously, since we have communicated that we will have a global study, there are other regulatory authorities where we will also need to have some advice. But first, we are going to finalize and take what FDA has recommended us to move forward and to prepare the IND and so on. The other regulatory authorities will come at the next step.
Okay.
Clas, just because it goes without saying, I mean, in order to start the study in the countries where we need to start the study or want to include, including UK, Spain, and other European countries, there also needs to be national approvals, of sort of study design, et cetera. So,
Yes
... so that will happen in the second half of the year as well, of course.
Yes, when do you expect you could finalize the protocol for the study?
Very soon, we hope.
Okay.
But yeah, so this is the thing. First, that is what Jens presented. First, you need to select your CRO, because-
Mm
The final development of the protocol is done together with the CRO. So in line with that, we are finalizing the protocol. We are also preparing for the IND submission. That goes hand in hand.
That's why, that's why we made that sort of box a little bit green today, to signal that-
Yeah
We are quite close on that.
Okay. And at that time point, we might also get a better indication of how much the study might cost?
Yes.
Okay, perfect. And then my final question is just if you perhaps are able to provide any update about the partnering process for fostrox.
Yeah, I mean, sort of. As we've said, previously, we've we initiated sort of the partnering sort of towards end of last year. We continue to have partnering discussions and sort of fruitful partnering discussions, and we will never comment on any details, sort of, until we've gotten to the point where sort of there is an agreement in place. But clearly, finalizing discussions with the FDA and getting clarity on study design and getting confirmation that, yes, sort of, this is the way forward, is also an important element because U.S. will be an important part of any discussions moving forward as well, to make sure that they are in the study.
So they are progressing and we're comfortable with all those discussions, and then we will, as soon as we have kind of details that are confirmed, then we will communicate.
Okay. Thank you so much. That was all for me.
The next question comes from Niklas Elmhammer, from Carlsquare. Please go ahead.
Yes, hello. Connecting to hear about the continued development in the combination study. I was just having a follow-up questions to the previous ones, regarding the FDA interactions, so to speak. What kind of feedback or confirmation have you had that proposed Phase two B will actually serve as a basis for accelerated approval at this stage? Or is this subject for future meetings with the FDA?
So accelerated approval is granted depending on the results from the clinical trial. So FDA can never say you are going to get accelerated approval on this. What they can recommend and guide you in is more, how should a study look like for you to create the evidence you potentially need for getting, first of all, a final approval, but also if the data looks good enough, if the unmet need is high enough, what kind of endpoint would be what you usually use for an accelerated approval in this indication? That is what they can say. And also, as we changed a little bit around the dosing, what would be required? What is the minimum thing that you actually need to have in place before you can go and submit for an accelerated approval?
That is the kind of guidance we can get from the FDA. They can never say this is enough for an accelerated approval before seeing the data.
I think that, maybe thank you, thank you for asking the question, because I think this is an important element. After in a Phase 2, as you move into a regular Phase 3, there will be discussions, dialogue with the FDA to, to agree on sort of is a Phase 3, a registration enabling study. So, so that's a conversation that you do have when it comes to Phase 3. But for accelerated approval, it doesn't work like that. Sort of, you can only have sort of discussions and get feedback from the FDA on, on yeah, okay, well, get guidance on what are the most appropriate endpoints and what do you need to do to kind of strengthen your chances.
And this is, for example, one of the reasons why it just became clear in the conversation that, yes, we believe that PFS is perhaps, maybe a slightly better endpoint, and the experts are saying so. And we could go ahead with PFS as a primary endpoint for the study, but the conversation with the FDA made it clear that, yeah, it may be that you think so, but sort of ORR is what they have used and what they accept as a surrogate endpoint for accelerated approval. And then it's up to us to sort of take that guidance and implement it. It becomes relatively simple for us to do it because this is our aim. But as Pia said, there will not be a formal, okay, well, now, as long as you hit your primary endpoint, this will gain accelerated approval.
Okay, thank you. Great.
As a reminder, if you wish to ask a question, please dial pound key five on your telephone keypad. The next question comes from Hans Englund from private investor. Please go ahead.
Hello, guys. In terms of the presentation at ESMO, when will be the break time for those data that will be presented?
Actually, this is more related to pharmacodynamics. Fredrik, do you want to respond to that question?
Yes. So, the main part of this presentation at ESMO GI is liver pharmacodynamics. So that will include all biopsy data that we have gathered during this Phase 2a study.
So there will not-
Okay.
Yeah.
I got the impression from what you wrote that you would present sort of total-
Yeah
-data to...
We would present that as well, updated data, and that as this is an open label, right? We will try to present the data. We will get to confirmed, since now we have an accepted abstract, right? The data might have improved even further when we provide the presentation. So we will present the data that we can present, with quality, at the latest time point for the Congress.
I mean, Hans, there's always a bit of the data needs to be sorted for, as we go to a Congress, to make sure the proper sort of cleaning is done, et cetera. Difficult to give an exact date, but there will definitely be later update than what we are sharing today. So any continued progress and strengthening of the data, that will sort of come through at the ESMO GI presentation.
Good. In terms of what you're reporting today, you're not reporting any ORR. As I looked at the slides from my phone, so I couldn't really see, but the PFS, the TTP data were from sometime in April, while the ORR data was from sometime in February, what I saw. Could you just comment on that?
Yeah, that is a mistake, actually. I'm sorry, but because it's from the same date, everything is from the same date, and the ORR is 24%. So we-
Okay.
Yeah. So, since the ORR comes earlier, you might say, than what we can see, for example, PFS, as we talked about before, that tend not to change too much after having a follow-up that is currently relatively long. It's more than half a year. So-
Okay
... It's more or less the same since we showed this, the last time. It might have changed in one or two of the patients, that the reduction has become a little bit bigger, but otherwise, it's the same data, 24% ORR.
Okay. When you spoke about the choice of ORR in Phase 2b, you said that it's usually chosen because it's sort of usually earlier.
Yes.
I understand that, but on the other hand, you often say that the effects of fostrox are increasing or could be increasing over time. Could you just elaborate on sort of those two statements and-
Yeah
How you look at that?
... Absolutely, and this is one of our concerns, because we do believe that with the mechanism of action of Fostrox, which is a nucleoside analog, it means that it's incorporated in the DNA in dividing cells. And since liver cancer, it's a heterogeneous disease, it could be different in different parts of the tumor. That's why we can see late responses with liver cancer. That doesn't mean that there are not early responses as well, because we have seen that, too. So it might be that we will miss one late responders when we look at the data initially. That's for sure, and that's why we were recommended to have progression-free survival, because then you are not dependent on, like, the response itself.
But again, when we chose to look at overall response rate in this Phase 2b study, that is the primary endpoint where you calculate the number of patients. That doesn't mean that all the other endpoints, as PFS, overall survival, duration of response, disease control rate, all of that will be looked at as well when you compare-
Mm
the outcomes between each other. This is just a matter of having a chance of having a significant result in the study.
Yeah. Okay, okay. Last question then, and that's the timing of the IND. What can we look forward to here in that respect in the U.S.?
So the timing of the IND, the IND will be submitted when the protocol is ready, coming back to Clas' question there.
Okay.
Since we needed to select the CRO first, which we were in the end stage of doing, yeah, relatively soon, I can say. It's a process that has started, and obviously, it's important to submit the IND, but that will not delay our study in any way. We are in good time to submit the IND to the U.S. for enrolling patients in the U.S.
Okay. And normally, how long time does the FDA take from they have gotten the protocol to decision on IND? Is it a 2-3 months process, or?
No, it's a quicker process. It's about-
Quicker? Okay.
Yeah, it's a quicker process. Oh, I thought it was one month, but don't quote me on that.
Okay, okay, okay, okay.
Yeah.
But it's a rather quick process.
Yeah, because-
Okay
... the IND is supposed to be there, so you can actually move your drug between the different states in the U.S., right? So it is a quick process.
Okay, okay. Well, by the way, one more question. In terms of the ongoing study, I sort of draw the conclusion that you wanted to have the final study ready by late this year, enabling you to sort of present the full results at ASCO in January. And you have a six-month review period, as far as I remember. Does this mean that you will probably sort of stop the study sometime in May or June, or what-
I think-
Sort of stop the thought, except for the six-month follow-up, so.
It's a good question. We can present data anyway from the study since it's an open label study. But the thing is, I think I said that as well, we were a little bit surprised that the patients just keep having benefit from the treatment. So the patients are ongoing longer than we expected. We didn't expect to have the study open this long.
Okay.
In order to make sure that we actually can provide this study treatment to the patients when they need it, we will keep the study ongoing for now, but we hope to be able to close it sometimes late year. But again, it depends a little bit on how many patients that are still ongoing in the study. So it's ongoing.
Okay.
Yeah, and there are some practical elements, because the one thing we need to do is to make sure that sort of whether we have the study open or not, as long as the a patient is benefiting from treatment, we need to find a way to supply that patient-
Yeah
... with the study drug. So, there can be some practical elements, sort of deciding or influencing exact timing of things.
Okay, okay. Thank you.
Thank you, Hans, for spotting that data cut off mistake on slide 9. We will adjust it when we update, upload the presentation. Just to be super clear, all the data presented here are using the same data cut-off date of April eighth.
Eight.
Whether it's ORR or TTP, et cetera. Do we have any more questions?
There are no more questions at this time, so I hand the conference back to the speakers for any closing comments.
Thank you very much. Thank you everyone for dialing in. Thank you for all the engaging questions. As we have said, we are super excited, of course, about the progress we've seen in other parts of the pipeline with MIV-711, for example, granted rare pediatric disease designation. But most importantly, as we move forward, again, to reiterate, we are highly excited about the potential and the progress we are seeing with Fostrox, the potential to improve second-line HCC therapy. Fostrox is the first and only smart chemotherapy, selectively killing cancer cells in the liver, and the results continue to strengthen, and even with that, we are today seeing a doubling of response rate and time to progression.
So we continue the plan as before, timelines as before, with the aim to become first approved treatment in a patient population worth $2.5 billion. So with that said, thank you everyone, and have a good rest of the day.