Hello, everyone, and welcome to the Buywika Capital Market Day of 2021. My name is Anders Schulander. I am the CEO of Buywika. And just a few words about my background, which is within Management Consultant, many years with Accenture and Entrepreneurship where I co founded management consulting company, Ax Holmen, which led to that I eventually came into contact with Buywika as an investor. And I was attracted by the great potential, both Human and Commercial.
And the fact that we with our product can be beneficial for cancer patient on treatment and also for payers and health care providers. We'll get more into detail into that today. So now today, I'm both the CEO and the main shareholder of the company. And talking about the agenda. And for today, we have 2.5 hours.
We'll go through, 1st of all, a company overview, which I will do. Then Doctor. Malorny from Peralta Hospital who will take us through the oncologist's perspective as he has great experience from working with the test in clinical trials. Following that, Charlotte Strangin will facilitate a Q and A before we go over to Amy Williams, our Scientific Director in U. S, I will be talking about the clinical utility for Divitum.
She will then be followed by our Senior Vice President for Marketing and U. S, Robert Dahn, who will talk about our go to market plan for our first application metastatic breast cancer in on the U. S. Market. Following that, Senior Vice President, Henrik Winter, heading up Business Development and Clinical Development, we'll talk about how we intend to expand outside our initial area.
And after short summary from me, we will open up for questions for the Q and A session, which will be facilitated by Charlotte Schengen. And you can also submit your questions. There is form on the screen that you can use and submit questions for the Q and A session. So I will start off my presentation with the current situation and the unmet need in metastatic breast cancer, but this is also valid for most metastatic cancer areas. And the good thing is for the patient that is that there are a lot of treatment options available, which has led to improved outcome for patients.
But it also creates a different problem of complexity as all patients does not respond to all treatments. And also over time treatment resistance is developed and it's important to be able to monitor treatment efficiency to follow-up and make sure that the patients are constantly on the best possible treatment. Currently today monitoring is done by Imaging Diagnostics and here's an area we think we can bring a superior solution to the benefits of patients and healthcare providers, which we will go into more detail. And how does that solution look like and what is it? Well, the product is called Divitum, stands for dividing tumor.
And that's an indication of what we do. We measure cell proliferation. And as you know, the way cancer growth is through cell proliferation. And we are able to measure this by measuring an enzyme which is prevalent in the patient's blood. So from a blood sample combined with our product that's implemented on a standard platform for EC rollout on the clinical labs out there.
We're able to give a value of how proliferative, how the cell division of the tumor, how fast it is, how quick the Cancer is growing how aggressive the disease is, a prognostic value. So we're measuring cell proliferation what eventually will become an increase in volume. And we're able we're shown in clinical trials that we can provide valuable information both before prognostic and during treatment. Currently, these patients are being monitored as a standard way of monitoring by image diagnostics, where you take an image before start of treatment and then during treatment and you compare the size of the tumor. In clinical trials, we've shown that we already 2 weeks after start of treatment, can provide feedback if the patient is responding if their levels are being significantly reduced.
And currently it requires 3 to 4 months before you can follow-up on using image diagnostics. Surgical Monitoring Technology. Imaging is a standard method, as I said, and it requires 3 to 4 months before you are able to follow-up. It also requires it's invasive and it requires patient logistics. You need to travel to these centers.
Imaging has other great benefits. You can see where the tumor sits and so on. But we believe that we are a great complement Sertool II Imaging within the field of monitoring. And the same goes for biopsies where you take a needle and you take a sample of the tumor you analyze that and you can do a lot of things with that. You can do proliferation market just like dividend and you can do gene sequences, look for mutations and so on.
So biopsies is a great tool to, for instance, predictably decide which treatment to use. But it has its shortcomings within monitoring, where you take serial testing. It's not used currently that way. And so for biopsies, we believe we also are a great complement. When it comes to blood based markers, we're more of a direct competitor.
But however, there are very few used in the monitoring field currently. There is examples like the CA15-three, but it's not being widely implemented and used due to some shortcomings. Not all patients are expressing this antigen that's measured. And performance wise, it hasn't proven itself either. Dividend has been compared once in the clinical trial from Karolinska, where we outperformed CA15.3.
There are also other new technologies. CTCs is one example or I would say newer because that has been around for quite some time now and has established itself within areas and more to determine risk for recurrence and progression rather than monitoring. So it's an earlier phase, you could say, of the treatment process. So not a direct competitor either. And that also goes for the newest technology of these mentioned, that's ctDNase, a really interesting technology.
You could do gene sequencing and mutation analysis not from a biopsy, but from a blood sample, which of course opens up a lot of opportunities. But at the same time, it has shortcomings that it requires a lot of blood and also is quite complex and costly. So the focus areas has more been into more predictive applications, and we don't see it as being used in monitoring either. So and we also see dividend as a good complement to CTCs and ctDNAs rather than competing products. So when you summarize the area, there's a lack of good blood based biomarkers for monitoring.
And so we believe that with DIVITUM and the data that we have generated so far, we have a really strong position within this area. Talking about the data that we have generated and the collaborations we've had with leading oncologist within the field like Doctor. Malorn, which will be following me and others. To date, we have 24 clinical trials that we have performed together with our collaborating partners that has been peer reviewed and published in scientific journals. And the majority of these is within our focus area, breast cancer.
Senior, but we also have proof of concept data within other important cancer areas like the gastrointestinal and lung cancer area, for example. And if you should summarize the results, you could say in metastatic breast cancer, where we have had access to serial samples, have been able 2 evaluate those. We've been able to monitor the treatment process and provide quick feedback on treatment efficiency. And in both early local cancer and metastatic cancer, we've shown that we can be prognostic before start up treatment, assessing risk for recurrence in the local setting and both progression and survival in the metastatic setting. And these results are consistent over several trials.
So it's important to generate the data, but it's also important who you work with and who will actually communicate the data to the scientific community and the other oncologists out there in this field. It started out with Karolinska in Sweden, where we now are working together with them in our 3rd trial. We shortly thereafter, we started our collaboration with the Prato Hospital and Doctor. Malarni and his team, and we have now done several collaborations together with that team. And we have also done a prospective in Europe with the BIG and IBC's G Group, which covers several countries in Europe.
And in U. S, we also have several collaborations with Washington University, Mayo Clinic, Baylor College, Johns Hopkins, etcetera, in different clinical trials, primarily within breast cancer. Going into the breast cancer area. This slide is a breakdown of the results so far. And as you can see, we have from early phase all the way to the metastatic setting, spot our focus area is the metastatic setting.
That's where we see an unmet need that we can meet, like I talked about previously. And we're now building a very solid set of documentation, which will be the foundation for the entire commercialization process. So you see the blue ones here are the one that has been completed and peer reviewed and published. The pink one has been completed and presented at different conferences, and you can expect them to soon be published. And then the white wines are the ongoing trials we are doing to strengthen our data and evidence of the potential and the value of the product.
And the reason we do that is to be able to bring the product to the market to clinical use and uptake. And these are the key activities. Of course, you have to have a product, which we now have a third version. And this last version that we have developed is specifically developed to meet the requirements of the FDA and the regulatory authorities. And the next one is the clinical development and documentation.
That's the clinical data that we have the work we've done using the product to document the performance and the value. Regulatory pathway is, of course, very important because without regulatory approval, you're not allowed to market and sell the product for clinical use. And as we are looking to launch to enter the U. S. Market, the 510 process by the FDA is our focus, and I'll get back S2 where we are in that process.
But regulatory approval is not enough. You need to make sure that this becomes standard part of the guidelines, the standard practice to use the product and also that you get paid for the product. And so the clinical data that we are generating is not only for regulatory use, it's also for guidelines reimbursement and also team with a commercial partner that can offer the product as a service, a lab that can provide the analysis and the response to the different treating physicians that need this information. And when we have all these pieces in place, we're ready to launch the product and that's what we intend to use later this year. We'll come back to that as well.
The FDA process. Yes, that's, of course, really important to us. And we have submitted our application already in Q3 last year. And we quickly passed the first two milestones in this process, which was very positive, before the FDA made a general change in the way they allocate their resources and choose to prioritize COVID related tests and put everything else on hold. So we also got put on hold and that was prolonged until January this year when they started to restart some of the processes, and we were lucky to be one of the selected processes that was restarted.
So we are very grateful for that. And since then, we've been working with the FDA in several rounds. We have answered questions and the process is progressing well. Although the FDA is clear that they have not committed to their normal standard time line, we see a slower process, but it still is progressing well. And that's why we keep our milestone that we expect to see a clearance of the product in the Q3 this year.
So I talked about the U. S. Market being the first one we intend to launch the product. And we have also estimated the market potential for Europe for U. S.
And then Europe as the second one, including the big five European countries and the Nordic countries, which are our focus areas and then the Japanese market as our 3rd step. And we also expect to be able to reuse a lot of the data, especially from the U. S. Launch to the European as the regulatory process, for instance, R and the treatment guidelines and so on are very similar. And going back to the market potential, those figures you see here on the market is based from market research that we've done, where we have interviewed payers for the value and the price sensitivity and key opinion leaders, oncologists for how they would use the product in the clinic, combined with the number of patients living with the disease.
And as you can see, the greatest potential is the U. S. Market because the market research indicates a price level, which is significantly higher than the European market and the Japanese market is somewhere in the middle. And in total, we estimate the total market potential for the breast cancer metastatic breast cancer monitoring market to US400 $1,000,000 to US700 $1,000,000 per year, we should say. Yes.
And to be able to execute on this plan, of course, you need to have a strong team with great experience from doing this previously. And so that we have this is our management team, where we have different functions the people that has done this before. So we have an experienced team, which just recently have been strengthened with Helly Fisker, which is the Commercial Director, started a couple of months ago. And also in the Board of Directors. We have people with great experience doing similar projects both within Diagnostics and Oncology Pharma that contributes secretary to the development of the product of the company.
Lars Hogfeiss, being the Chairman, has a history at the Darko, where he were the CEO and was part of the transaction when Agilent acquired Darko in a successful transaction. And the since then he's been part of several larger diagnostics and pharma companies, for instance, like Vitra Life and now Bivika. All of the Board of Directors have holdings in Baywica and most of the people in the management team as well. That was more or less my 20 minutes. And I'd like to hand over to Doctor.
Luka Malarni at the Prata Hospital in Italy. And Luka, please take us the
Hi, everyone. Just a brief introduction. I am Luca Malormi. I am the Director of the Translational spinal research lab here at the Hospital of Braco. I'm a medical oncologist.
And I am very much interested in translational research in oncology, and in particular, in biomarker development for breast cancer in particular. And for that particular breast cancer that expresses hormone receptors, which is, of course, as you may know, the most common subtype of breast cancer. So why I'm here today, and I think Anders made a great introduction to Mindslide, Because we have done quite a lot of work in collaboration with Biovica in the past few years the use of this dividend assay for research purposes. And I'd like to start the conversation with you about our experience with this dividend test. By starting with our very first publication we did back in 2018, I will go quite in some detail of this publication Because I think that most of the messages we want to give To oncologists and, of course, also to patients, are basically in this paper.
And the concepts that we developed during in this paper were then taken So if I can have the next slide, please. So the concept, as Anders was just saying a few minutes before is that this assay measures tumor proliferation. And the beauty of this assay is that it's very flexible. And you can, of course, for clinical purposes, you can do it the blood of the patient. But pre clinically, so in the lab, you can even use it in cellular models, and this is what we did to begin with, because we wanted to have proof of concept that breast cancer cells that respond to treatment actually have a response also a reduction also in this biomarker.
But when you do not see sensitivity of the drug, so when you have endocrine resistance, so cells that do not respond to endocrine treatment, you actually do not see an effect. And so we choose in the lab different models, those that are endocrine sensitive, so you give endocrine treatment and the cells start to reduce their proliferation and slowly dying. So you see an effect on tumor growth. And the endocrine resistant cell line, which is depicted here in red, When you do not see an effect of the endocrine treatment, and so you do not expect anything to happen when you treat So if I can have the next one, please. Next slide, please.
So On the top of this slide, you see the regular growth that is measured in the laboratory when you want to understand if cells are growing or not. And this is done basically by counting cells. So that's the top panel. On the lower panel, we have Divitone. So, you see that those 2 endocrine sensitive cell lines.
When treated with endocrine therapy, as expected, they both respond in the top panel. So you see a reduction in the number of cells, But you also see a reduction in DIVITUM. So DIVITUM means reflecting what the sensitivity of the drug, While you do not see an effect in the endocrine resistant cells, so they do not arrest their growth after endocrine treatment. And in this case, you do not see, divitum going down just because the cells are not responding. So you see a perfect reflection in Divitum of what is the behavior of the cells during treatment.
But the interesting thing is that, while you need many days to observe these changes in the upper panel, because We have to observe sales up to 6 to 9 days to see a decrease in cell number. Actually, with Divitum, you just need a couple of days because by day 2, and you see this is in the lower graph, You already understand which are the cells that will respond and those who will not to treatment. So you have an anticipation the So the first take and next slide, please. I just put some flashes in slides just to highlight the important thing that we learned from these experiments is that the reduction of TK activity, so in Divitum, after endocrine therapy is an early sign of response. Okay?
Next, please. Science. We wanted to see whether in patients, so in patients with metastatic breast cancer, hormone receptor positive, treated with endocrine therapy at our hospital if measuring Divitum was helpful in understanding which patients were going to respond and which patients won't be responding to end of end therapy. And so you see, we collected a small cohort of about 30 patients. So if I can have the next one, please.
Yes, this one. The first exactly, please. The first stake from this is that, as you can see from the numbers, but it's just easier if I can comment on that, We collected baseline samples, so before starting treatment, samples from same patients after 1 month of endocrine therapy. And then samples from the same patients when the disease was progressing. So when the treatment was failing, so when the patient was undergoing this progression.
And as you can see from the median levels of dividend, which is written in this table, the the starting point was quite high, 122, but then only after a month of treatment, it dropped significantly 2:36. And then when the patients were progressing, it increased again to 3:30. So the take from this first data was that the activity of TK1, so divitome output, is reduced by the treatment and that this increases again a disease progression. So it goes very well with the concept that This is seen very, very well here. You see that this is the what we call a spaghetti plot.
So these are patients, individual patients across 2 different time points. And this is in particular the early time points of 1 month after treatment. The starting point and the 1st month of treatment. And you see that most of the patients have a spaghetti that goes down, Which means that they were dropping their dividend levels. But you also observe that there are some, the blue ones who actually increase.
And if you look at the outcome of these patients,
the
The interesting observation was that most of the patients with an increase during that 1st month of treatment Where patients who actually were not responding to the therapy. And if I can have the next one, please. This is very well depicted by this plot where you see that those patients with an early drop of Divitome after only 1 month of treatment at a very well very good outcome because they had a median progression free survival, which is the metrics We use in the clinic to understand, for how long a patient benefits from a treatment, which is quite long. It's 14 months. And this is only using hormonal classical hormonal therapy.
While those patients who had, in that 1st month of therapy, An increase in DVTUM. They had a very short progression survival probability of only about 4 months. So you see, this is a substantial difference. This was, Not only we observe early changes in responding patients, but that this early response It's very clinically informative because only after 1 month of therapy, in this case, we can have long term information
the
because not only the difference between the baseline and 1 month, so the change was informative, But also the actual baseline level. So if we stratify patients for their baseline, so before starting treatment, dividend levels, we We see that those with high levels have a worse outcome as compared to those with the lowest level. So this is also important because we are always looking in the clinic for prognostic markers or those markers that can give us information on the prognosis of the patients and on the characteristics of the patients that leads to an early failure of treatment versus a longer benefit. And actually, in this small cohort, we saw the very good prognostic value for baseline also, dividend levels. Next one, please.
So this was a first and initial experience, and I think it was very positive. All the answers we wanted to have different studies to actually believe that what we were saying in a smaller study was actually replicated. And this is what we did In a subsequent publication. If I can have the next one, please. We were able to collaborate with AstraZeneca, and they gave us access 2 this Phase III trial was called EfkT.
This is a trial that was comparing 2 different kinds of hormonal therapy for metastatic disease. And as you can see, in this study, we had a much larger sample size because it was 30 something patients in the previous study. Here, We have about 200 or more. And even in this case, we have baseline and also subsequent samples. Next one, please.
I will go very brief on that just because this completely confirmed what we have seen in the previous study in a larger sample set. You see that on the left hand side of the screen, baseline dividend levels were very good prognostic indicator, but also the change between the baseline and the 3 months in this case, because this was the earliest time point that was collected in the study after baseline. So it's not that early as the 1 month we have seen in the previous one, but this is the best we could get. The The change between baseline and 3 months was also very informative. So those patients who had a decrease in those 3 months individual, did much better than those patients that actually had a stable or an increased, divitum across the first three months of treatment.
Next, please. So the final take is very easy that the study fully confirmed what we expected in the smallest previous study. Next one, please. So then we moved to a different scenario. So by the time We had done this first experience, CDK4six inhibitors, a new class of drugs, head become the standard of treatment.
So, now we don't treat patients any longer with single agent hormonal therapy, the good biomarker also in this setting. And this is why we applied dividend to a cohort of patients that we had treated in a clinical trial here in Italy, a clinical trial that was conducted primarily by us here in Prato. And so we made a substudy in this clinical trial that is called TREND with Divitum. Next, please. So just to have a sense, whether Divitum was going to be a good biomarker in this setting.
We took advantage of our laboratory and so all the models that we generated in the lab have acquired resistance to this new class of drugs. And just to make a long story short, we realized that the timid Encounters 1, which is the gene is one of the top differentially expressed genes in between sensitive and resistant model. This means that when the cells become resistant to this new class of drug, they have an increase in TK1 levels. And so we argued that the increase in TK1 levels would also reflect in an increase in DVTOM activity. So next one, please.
So we went back to the models that I showed you in the first study And we compared what happens in sensitive cell lines to CDK4six inhibitors and in resistant cell lines. To make a long story short, you see that even in this case, Divitum can capture sensitivity to the drug and also resistance, because in resistance models, you treat with a drug and you do not see any change in Divitum levels, while you do see an early response of give it home in responding centers. So this convinced us that not only in the hormonal therapy alone, but also in the hormonal therapy plus CDK4six inhibitors, the new standard of therapy, Divitum was going to be an effective biomarker. And this is why, next slide, please. Next one, please.
We applied digital to samples taken in this study, which is called TREND, as I told you. Next, please. Even in this case, we show that the dynamic change, so the change between baseline and in this case, also a month after initiating treatment. So, it was very clinically informative because, those patients who actually had an increase of TK activity during this 1st month of therapy, had a very bad outcome. You can see from this black cohort that this patient really do not benefit from the treatment, while those patients who had a decrease individual during this month of therapy had a better outcome.
So this told us that what we had seen In the previous studies in organelle therapy alone, did also apply to the standard of therapy with CDK4six inhibitors. Next one, please. Next one, please. So this prompted us to study this in a larger population. This is a multi center study that we conducted in collaboration with International Breast Cancer Study Group and the Breast International Group.
There are 2 important international cooperative groups for the study of breast cancer. This study is called PITIA, and it's a Phase 2 biomarker study that was developed the with the aim of looking into new biomarkers of sensitivity and resistance 2 CDK4six inhibitor and in particular to palbocaglabi, which is one of the first CDK4six inhibitor that was marketed a few years back. And if I can have the next one, please. Also in this case, we collected samples Across multiple time points, in particular, there was a baseline, like in the other studies. But unlike the other studies, in this case, we had a very early time point, So only 15 days of treatment, while in the others, we only had the 1 month.
And then we also had the day 28, so a month of treatment. So we have this intermediate time point on day 15, which we had never observed in the past. And as you can see from this spaghetti plot, you see here now more spaghetti because there's more patients. This is a study of 122 patients. But you do see this pattern that most of the patients do have a response.
And you see the median goes from 87 from baseline to 18. 18 means that, so this is kind of technical, but This dividend assay has a level beneath A level of detection, we call it limit of detection. Underneath this limit, the The test is basically completely negative. It's almost like it's undetectable. So it's so low that you have to say that it's undetectable.
Okay. And you see that in a lot of patients, after 15 days of treatment, this dividend went so much down that it was undetectable because it was below 20. And then you had somehow a rebound at day 28 of cycle 1, so after a week. And this is because and I haven't told you this because this is kind of technical, but the The reason why there is this rebound is that the palbociclib, the CDK4six inhibitor we were giving to patients in this study It's dosed with a schedule that is 3 weeks on and 1 week off. So during this Day 15 and Day 28, there was a week of therapy that probably allowed the cells Of course, this schedule in the clinic is given for toxicity issues, so we cannot But it's very interesting that this assay is so sensitive that can actually capture the small differences during such short windows of time.
And if I can have the next one, please. So the question was, we see a reduction at day 15, small rebound on day 28, but is this clinically informative? So let's start from the baseline. Like in the other studies, We see that baseline levels are very informative because patients who start off with low Divitum levels do much better than patients who start off with higher levels. And this is kind of confirmatory of what we had seen before.
But again, this is very important because patients in the good group, so those who have low TK to begin with, have 17 months of benefit from treatment, while those in the high group have only about 7 months. So it's Very different in terms of treatment activity. Next, please. But what was most striking is the effect at day 15. So those patients who went Under the limit of detection at day 15, had a very, very good outcome.
You see here, It's depicted in the red line or they are called low patients. They have 16 months of median progression free survival. While those patients who do not have this reduction after 15 days of treatment have a very bad outcome of about 5 months. And if you see the blue curve that depicts these patients, You see that, again, around 6 months of treatment, most of these patients are progressed, Which is a very bad outcome for this class of drugs, which overall is intended to control treatment Can I have the next one, please? Also, Day 28 was also very informative.
And you can still see this very good prognostic role even at day 28. Next one, please. So these results that I just shown you were presented at the San Antonio Breast Cancer Symposium last year, and we are now in the phase IBCS GmbH of writing the manuscript. We should be ready for submission very soon. But in the meantime, we have continued our experience.
And these are there are 2 relevant next steps which I want to share with you. One is this Bio Italy trial. This is a large trial of about 300 patients that are treated with hormone therapy and a different CDK for 6 inhibitors compared to the one that I just showed in the previous trial. This is ribociclib, and this is produced by Novartis. And this is a Novartis sponsored trial, but they They asked us, to begin with, to be in the steering committee of the study, and we suggested to include Divitum into this trial because the aim of this trial again was to look for biomarkers of sensitivity and resistance to ribosaglib and hormonal therapy.
And so this is being implemented the prospectively in this trial from the beginning. And as you can see from this graphic here, Also in this case, we will have baseline, day 15, day 28, first team at Jynne, and then we have disease progression. So there's a lot the more to learn in this study. And so we aim here both to confirm our previous data, But also to deepen our understanding on the use of dividend also at different time points. And for example, to understand also what happens in those patients who respond at day 15, but then they rebound at day 28.
So things that we could not look for in the previous studies because there were few patients. But now with the sample size, they're so big. Of course, we can do that. And the next slide, please. And then the other study That we are conducting.
This is called Tiresias. This is a study that it's an Italian trial that we are running from a year or so. And as you can see, also here, the concept is to collect a lot of different samples to understand the mechanism of sensitivity and resistance to CDK VAR6 inhibitors. And Divitum is one of the main study endpoints. And also in this case, as you can see, we will extensively collect samples during the treatment with hormonal therapy and CDK4six inhibitors.
But also, we will collect samples from the patients after progression through this first line of therapy, in their second line of therapy. Of course, at that point, there's no mandated treatment to give, but the treatment is left to discretion of the treating physician. So we will see also the added value of using DVTomb in other treatment contexts after failure of CDK4six inhibitors, which are the standard of care, as I told you, in the first line setting. And with the next
Thank you. Thank you very much, Doctor. Malarni. Those results that you have presented Very impressive. My first question would be, how would you use Dividend in your clinical in your daily practice given these fantastic results.
Yes, thank you for the question. I think it's Very easy. Yes, sir. Just to speak of what I have already I've just shown. So it looks like Divitum can capture some biology in the tumor at Whatever time point you measure it, even at baseline or during treatment or after treatment, the The results we have seen in our hands, but also in other studies, clearly says that.
And this is very, very much in line with the biology of tumors, of breast tumors that we know. Proliferation is very important to distinguish aggressive tumors in breast cancer from less aggressive ones. And so this is it makes a lot of sense that if you can measure proliferation at any given time point. This is going to give you a strong prognostic information. I would use, in if I could use Divitome in my daily practice, I would use it as the baseline characterization of the patients.
So patients comes in, I get to know her, I collect the clinical history, the past history. The all the prognostic information that I can get from, the tumor biopsy, the previous treatment and so on. And I will add also this to the list of things to look for Because this gives a very good sense of where the patients sit in terms of prognosis. And this, of course, would help in choosing treatment because if I understand that the patient is In a poor prognostic group, maybe I would choose a more aggressive treatment as compared to a less aggressive treatment if I understand This patient is in a low prognostic group. But I think the most exciting and most important application for this in the clinic would be the on treatment evaluation.
So the fact that In only 2 weeks of therapy, you can have an information on how the patient will CEO in the next month. It's very important because we currently, we lack This information completely. So if we can substitute the baseline evaluation with the A number of different clinical information that we can get from the patients. We have nothing the response that we can see. And I think we have tested this now, as I showed you, Both with hormonal therapy alone and hormonal therapy in combination with CDK4six inhibitors.
But I think, and of course, I have no proof to say that, but I can guess that Most of the therapies, especially the targeted therapies, will be suitable for I mean, maybe to would be suitable for monitoring response in most of the treatment that we use in metastatic breast cancer. So also other treatments which are not endocrine or CDK4six inhibitors. And so I think this is very, very helpful because it reassures the clinician as well as the patient that the treatment is working and that will work. And so I think that if I had a chance to use it in the clinic, For sure, I will do it the baseline and on treatment evaluation to understand the prognosis and the response
It really sounds like Divitim can be clinically useful. So, I'm glad to hear that. But you also mentioned that you lack tools today. Aren't there tools like ctDNA today? What is your view on that?
So it's true, there are other because you know that ctDNA, so the circulating tumor DNA that you can find in the blood with a liquid biopsy, the so called liquid biopsy, is not found in every patient. So not every patient has enough circulating DNA that can be measured. And not less importantly, Even if ctDNA is there, not every patient has a mutation In the ctDNA, that is clinically relevant, that gives clinical information. So it's, I think, a completely different story, the liquid biopsy for genomic purposes. That's very important when you have a drug target that you have to find in order to give a specific drug.
And for these patients, the the only example is the mutations in the PIKTRCA genes, which allows you to give a specific drug that is, Alpellisib, the P3CA inhibitor. But other than that, there is not an added clinical value in knowing if a patient has a certain mutation or a different one. And on top of that, of course, it's not clear whether you can confidently use changes during treatment of ctDNA to understand if the patients are responding or not. So in other words, ctDNA, it's important For precision medicine, when you have a target and the metastatic breast cancer, hormone receptor positive, HER2 negative, it's one drug only, No more than that. And, but it's very limited potential to monitor disease.
And even in the best scenario where a patient has ctDNA and you can monitor that during treatment, This is not for every patient. Only a fraction of patients will be ctDNA positive, will have mutation to detect. While with Dimitung, we always had in all our trials results for each individual patient. So Every patient gets a result for Dimitome. Every patient gets a result that is clinically relevant,
Clinically relevant results. We like that very much. Thank you very much, Doctor. Now we are going to leave the word to Amy Williams. Please go ahead, Amy.
Thank you. Good day everyone. My name is Amy Williams. I'm a cell biologist by training with a PhD in pathology. And I've worked in cancer drug development at several major pharmaceutical companies for over 2 decades.
The most recent company was Novartis, where I helped launch new breast cancer drugs in the U. S. These launch experiences highlighted for me the tremendous value of physician medicine in guiding treatment decisions for oncologists and in improving cancer care for patients. I joined Biovica in February because of the company's focus on precision medicine and the novel opportunities with Divitum. I'll be sharing with you where we see Divotum having an immediate positive impact on patient care And providing a solution to unmet clinical needs important to payers, patients and physicians.
Next slide, please. The data that we've generated with Divitum through our clinical trial program has the potential to impact current clinical practice for metastatic breast cancer patient care. In the next several slides, I will review how we intend to transform clinical research into clinical practice. Next slide, please. We envision 2 ways that Divitsum could be integrated into routine clinical care of patients with metastatic breast cancer Based on our observations from the research data, the first utility is as a disease monitoring tool.
Divitum provides information about the level of tumor cell proliferation and growth, which is really the key piece of information you want to know when monitoring metastatic tumors because Divitum can provide this information in a relatively rapid, convenient and non invasive way. We believe that it has the potential to reduce the frequency of other tumor monitoring methods, such as imaging scans that are less convenient, more costly and possibly less accurate. The The second clinical utility for Divitum is to identify as early as possible patients whose tumors are intrinsically resistant to treatment So that the ineffective drugs can be stopped and the patient can be given the opportunity to receive a medication, which is effective, Thereby avoiding the additional toxicity, cost and time spent on a futile therapy. Next slide. As I mentioned on the previous slide, the first current practice we intend to change is the frequency of imaging scans.
Computed tomography or CT scans for short and bone scans are the predominant methods used in clinical practice to monitor tumor response and progression during the course of therapy. The optimal frequency of imaging is uncertain and is primarily based on the monitoring requirements used in breast cancer clinical trials, which mandates scanning all patients for progressive disease about every 2 to 3 months. So in the absence of any robust evidence to perform scans more or less frequently than that, most oncologists routinely scan their metastatic breast cancer patients every 3 months. Our clinical trial data suggests that a significant number of breast cancer patients who are responding well to therapy likely do not need to have a CT scan every 3 months And could be monitored by assessment of thymidine kinase activity instead. On this slide is data from an actual patient on a clinical trial Where the patient had imaging scans done every 3 months and had blood drawn at the same time for TK activity analysis with Divitum.
This patient had stable disease for 33 cycles of therapy, so almost 3 years until progression was detected by a CT scan. Below the arrow, you can see the corresponding thymidine kinase activity levels. The levels are very low until around Cycle 28, where there is a 5 fold increase as compared to the prior reading. This increase in tumor proliferation activity section of tumor growth by divotum versus by an imaging scan is about 80 days. Next slide.
Translating this observation into clinical practice could look like a clinician deciding to maybe skip every other imaging scan in a patient with repeatedly low thymidine kinase activity values. Next slide. Or a clinician could opt for just an annual imaging scan in a patient with repetitively low TK Activity Values and No Clinical Symptoms of Disease Progression. Both options could potentially reduce healthcare costs And mean less inconvenience for patients. All right.
So I've told you about the potential for reducing imaging. Now I will talk the other key utility for Divitum, which is to quickly identify when a therapy is not working. Next slide. So predicting which cancer therapy is best for a particular patient is sometimes like having to pick from 2 unmarked paths in the woods without a guidepost to provide direction. You just have to start walking down one of the paths And you won't learn if you've chosen the right one until you've been on that path for months.
Divitum offers patients and oncologists a sign that they are on the right path just 2 weeks into the journey instead of 3 to 6 months. And here's an illustration of how this would look in the clinic. On this slide, you have 2 hypothetical hormone receptor positive metastatic breast cancer patients with tumors that from outward appearances look very similar to the oncologist. They might be the same size, the same molecular subtype in the same location. Yet the fate of these two tumors is very different and has already been predetermined by the unique intrinsic biology and genetics within each tumor.
1 will respond well to a CDK4six inhibitor and the other hat is what is called primary resistance And from day 1, we'll continue to grow despite treatment with the drug. This class of drugs known as CDK4six inhibitors, as Doctor. Malorny explained, are the standard of care first line therapies 4 hormone receptor positive metastatic breast cancer patients in the U. S. And in many other countries.
These drugs are given in combination with an endocrine therapy and many patients do quite well. The median time on this combination of drugs is about 2 years, with some patients having an extended benefit of 3 years or more. 15% to 20% of hormone receptor positive breast cancer patients will have primary resistance to CDK4six inhibition, Which means their tumor will not respond at all to the medication and will show progression within 3 to 6 months of starting therapy. Right now, on day 1, there is no way to differentiate patient A's tumor from patient B's tumor as far as predicting whether that tumor will be sensitive or resistant to CDK4six inhibitor based therapy. The only way to find out is to start the patient on therapy and wait to see what happens.
We know, as you just heard from Doctor. Malorny, that if you use Divotem to test for thymidine kinase activity before starting treatment with a CDK4six 6 inhibitor. And then again, 2 weeks into treatment, you will see 1 of 2 profiles shown on the left side of the slide. In the treatment resistant tumor on the top patient A, the level of thymidine kinase activity will show little or no change as compared the baseline TK activity level and may even potentially rise. Yet it could take 6 months or more to detect an increase in tumor volume significant enough to be visible on a CT scan.
In contrast, the treatment sensitive tumor on the bottom, patient B, will have a decrease in TK activity when treated with a CDK4six inhibitor indicating that the tumor has undergone a complete cell cycle arrest and is no longer dividing. Next slide. The clinical benefit of quickly differentiating a treatment resistant tumor from a treatment sensitive tumor is to be able to act on this knowledge and stop the futile therapy, avoiding unnecessary costs Antoxicities to the patient and potentially offering the chance to switch to a therapy that the tumor will respond to, leading to a better outcome for the patient. And of course, there's no guarantee that the next therapy will work. But the question you have to ask is, Why would you keep a patient on a drug that you know is not working and continue to spend healthcare dollars?
We are planning studies right now to refine the sensitivity and predictive value of our assay for exactly this purpose. Next slide, please. So to better understand these opportunities to impact and improve patient care, we have a number of ongoing and and studies which are outlined here. For monitoring disease stability, we are participating in a 100 patient study at Christie Hospital in the UK as well as several cancer centers in Sweden, which will determine the optimal frequency and timing for divotum testing and metastatic breast cancer patients receiving CDK4six inhibitor based therapy. We are also planning 2 new studies in the U.
S. To look specifically at how the routine use of Divitum to measure TK activity reduces the use of imaging scans. Additionally, we have partnered with, one of the largest cancer centers in the U. S. To acquire serum samples from metastatic breast cancer patients receiving standard of care therapy.
We will use this data to optimize and align the usage of Divitum with real world patient care. The ability to personalize medicine and match each patient to the best treatment for their particular tumor is always a goal with oncology medicines. To help with that goal, we have partnered with John Hopkins on a trial that they are doing, looking at the use of Divitum and other biomarkers to predict resistance to palbociclib plus aromatase inhibitors for metastatic breast cancer. We will take this finding one step further and design additional studies that not only use Dimetin kinase activity as an on treatment biomarker to identify resistant tumors, but to also potentially guide oncologists to a more efficacious therapy choice Based on the proliferative properties of each patient's disease. Thank you for your attention.
I will now turn the presentation over to Robert Dann, our Senior Vice President of Marketing and Business Development in the U. S. For BioVica.
Thank you, Eeli. As background, prior to BioVica, my experience covers big pharma at AstraZeneca, imaging diagnostics at GE Healthcare and artificial intelligence in healthcare at IBM Watson Health. Most of my work is either directly or indirectly focused on cancer care. And I joined BioVica as a clear opportunity To make a difference to the lives of cancer patients. If we go to the next slide, please.
So I'll cover several topics within our strategy and plans for launch in the USA. First, I'd like to give you a greater sense of the patients where we see Divitum as a useful aid to their care. I want to share the demographics And also profiles of typical patients where Divotome could be relevant. Next, I'll share plans for creating market access to the test. We've made good progress in the last 12 months in this area.
Then we can look at details of go to market plans, both for reaching key stakeholders and our plan of activities. I'll close with our latest views on expected test uptake from the US launch in metastatic breast cancer. Next slide, please. Here is the definition of the population whose needs we are addressing. We start with the number of new cases each year reaching a diagnosis of metastatic breast cancer.
That's about 57,000 women. Within that, the patient's disease, as Doctor. Malorny indicated, should be suitable for treatment with endocrine based therapies and postmenopausal. These filters bring the target population to 31,000 new cases arriving each senior at this point in care. These 31,000 patients can each receive up to 3 lines of endocrine based therapy in a sequence.
Median time on treatment for the first therapy, as Amy indicated, is about 2 years, and it drops to about 6 months for 3rd line treatment. For all the time while the patient is being treated with one of these therapies, Divitone can be a part of a disease monitoring strategy. Notably, the cost of some therapies used in this sequence exceeds $10,000 per patient per month. That's important when thinking about time spent on the therapy that is not actually working. In a budget And revenue driven system like U.
S. Healthcare, where patients often pay a portion of the costs, value for time and money is important to everyone in the system. Next slide, please. Demographics are important, but So are the profiles of individual patients, because it's individual patients where we aim to make a positive difference. First patient.
Let's call her missus Jones. First diagnosed with early breast cancer 7 years ago, treated successfully, but now her disease has recurred. She has a very active life and does not want her disease or her care to be a big interference. She will probably do well on her treatment, so minimizing the burden of monitoring is important. Missus Smith, on the other hand, may have more aggressive disease.
Her general health status is not great, but she wants to live well As long as reasonably possible. The choice of treatment, finding one that truly helps her is everything. Last, From the clinical characteristics of these patients, one might conclude that missus Jones is apparently one profile of patients and missus Smith is another. But during treatment, these profiles can change. Missus Jones' disease can become resistant to treatment, and missus Smith Can have a good treatment response and feel stronger.
That is why accurate monitoring of cancer cell proliferation is important. Divitum can help clarify these patients' disease status easily and regularly. Next slide, please. I want to change topics to the details of market access. Reimbursement in the U.
S. Requires 3 things: coding, coverage and payment, and those are the tickets to success. For coding, we intend to follow a value based approach, Initially, with a general code and over time moving to a specific code. For coverage of a test like Divotome, published clinical evidence, guidelines language and even physician pressure are all drivers. Payment at a favorable rate is helped by a budget impact assessment.
Unvalidated models developed by industry do not carry much weight, So we commissioned an external assessment that was recently presented at a major health outcomes conference, and I can share the results today. Top line inclusion of Divotome in the care path can lead to a positive economic outcome by simplifying disease monitoring And by identifying treatment resistance. Next slide, please. There are several incremental steps towards success to both inclusion in the guidelines and to payer coverage. Following the boxes from left to right, We can see both the position in the guidelines and the associated coverage outcome for DIVITA.
For a new test, at step 1, there is no mention of the test in the guidelines. For a test that does not have a major budget impact, Often because the test is for a restricted population, some payers will even cover it from this point. As evidence grows for a test, step 2. There could be a mention in the narrative of a guideline, but without changes to the care path. This will lead to coverage in a greater number of payers.
With evidence of clinical utility, step 3, The test is specifically included in the care path. Payer coverage becomes routine with test usage then dependent on physician adoption. In the most advanced scenario, step 4, the test becomes a requirement, a gate by the payers, before the next step in care. With this, coverage is very strong, and payers use this as a pressure mechanism on physicians to order the test the before authorizing anything more in care. For this last step, evidence of utility needs to be very strong with an example being HER2 testing in breast cancer.
Next slide, please. Let's look more closely at what the guidelines say today. Unlike typical guidelines for therapeutics, the monitoring guidelines for metastatic breast cancer are not very definitive, giving ranges for scheduling And allowing for some tests, as you see, as clinically indicated. 2nd, the monitoring pattern probably contains redundancies, As no single test today always gives a definitive answer, the recommendations are to do many tests with frequent repetition. This is challenging, as in particular, imaging tests can be a burden on patients.
Importantly, there is a usable category for Divotum tumor markers from day 1. This will facilitate payment. With time, as the studies that Amy described are completed, We will aim for a new category in the guidelines that differentiates Divotone from other tumor markers. These study results Should also help support relaxation of the scheduling of some other tests, such as imaging, even within the range of the guidelines today. Longer term, we aim to impact the language on therapy continuation in circumstances of TKA not being suppressed, But that will come with additional data and evidence and follows very strongly the directions that you heard from Doctor.
Malorny in terms of on treatment monitoring. Next slide. I want to look at the results from the budget impact model representing the potential impact on health care costs. The model was created by a team of health economists at the University of Washington, Fred Hutchison Cancer Research center. It first examines current costs for care of metastatic breast cancer patients, then introduces Divotum in 2 scenarios.
The The first scenario focuses only on changes to monitoring. The second scenario includes this, plus the impact of identification of treatment resistance early in care. Data sources are from published clinical research and epidemiology studies. In scenario 1, the clinical consequence of introducing Divotum into practice is that the frequency of imaging exams is reduced by about 50%. In scenario 2, in patients with primary resistance to CDK foursix inhibitor therapy, treatment is switched earlier than it otherwise would have been.
The financial consequences are that the addition of Divitum results in savings, About $3 for every $1 spent on Divotan. As health economic outcomes go, this is a very positive result Next slide, please. Looking at our plans around launch and our specificity for commercial targeting. Thought leadership and changes in clinical practice primarily originate in the U. S.
From the 71 NCI designated cancer centers. You see them marked on this map. Additionally, many of these hospitals have large clinical laboratories as part of their facilities. Separate from the hospitals, you also see a number of independent reference laboratories specializing in oncology. These labs serve both the major hospitals and the many community hospitals in the US.
While there are other oncology reference laboratories beyond this list. It is not a large group. And last, there is an interconnected group of payers and integrated delivery networks. You see a few examples of these on the right. For all of these, there are a few key takeaways.
One is that the number of key stakeholders is not very large. This enables us to provide solutions to fit individual needs. Second, these are not simply end customers that we will sell at. We intend to partner with these organizations on further research, Perhaps on risk sharing and on providing the best information possible from Divitum into clinical practice. Next slide, please.
To support commercialization and our interactions with a limited number of customers and partners, we are putting in place regional managers who will collaborate with opinion leaders, manage land partnerships and work with the payers in that region. You can See the intended regional structure in the chart. We are developing a small central team to deliver national activities. You have just met Amy, our Scientific Director. Team activities include clinical studies here in the U.
S, participation in major scientific events, message development and communication and development of the justifications In further developing the clinical evidence and science for Divotome and continue to expand our KOL network. I've mentioned partnering before. We are in discussions with potential partners to define roles. As agreements take shape over the coming months, We will share details. Next slide, please.
This chart gives a picture of the key events and ongoing activities for the next 12 to 18 months. Anders has touched on the regulatory plan and expected path to initial clearance and beyond. There will be several key publications and presentations over the coming months that support the clinical validity of the test And its economic impact. The study with Swag that we've talked about earlier has formed the clinical basis for our regulatory submission. We are expanding our interactions with key opinion leaders and hope to be able to share news of new collaborations soon.
As for ongoing activities, I've shared details of the commercial organization we're putting in place and the activities we need the team to perform. Development of this organization and its capabilities is underway so that we can adequately address needs of stakeholders. Next slide, please. Want to turn to expected revenues and test uptake. Earlier, I shared the profile of the 31,000 new arrivals in metastatic breast cancer each year that we aim to benefit from launch.
With Divicaton TKA in clinical practice, usage can also start during the course of approximately during the whole of the 3 and a half years that a patient may receive endocrine based treatment and not just at initiation of first line therapy. Advice from key opinion leaders suggest monthly treat testing with Divotum during the early period of a line of treatment And then reducing to 3 monthly until disease progression. This creates, in total, an opportunity of 750,000 tests per year. The To note, the number of test opportunities is slightly higher than we've shown in previous presentations. The change covers the advice from oncologists Doctor.
Maborny, where they want to add this test at 2 weeks after the start of therapy to assess likely treatment response or resistance. Several other factors will influence usage of Divitum as we establish the test. This includes market access factors, physician response to the test, And appearance of competitor tests. With the help of the budget impact model and payer advice, we can also now be more specific on the likely price for the test. So by the 3rd full year sales, we expect use in about 15% of eligible cases Within use in nearly 50% of test opportunities about 10 years from launch.
Beyond initial launch, there are potential expansions to the target population, which Henrik will talk more about going forward. Thank you. And I'd like to hand over to Henrik
the Thank you very much, Robert. So my name is Henrik Winter, and I'm overseeing the business development at Bayer Wicker. I have a background as a PhD and also associate professorship within cell and tissue biology. On top of that, I have 20 plus years within the diagnostic industry, part of that overseeing divisions at Darko and Adjuvant Technologies, especially the companion diagnostic divisions. I joined Biowica approximately 1.5 years ago, And I was very curious to know and learn more about the TKA biomarker because I think it has potential within the monitoring of treatment.
So over the next approximately 20 minutes, I'll cover the following topics. You can see here. I'll dive into the next indications We are to pursue with our Divitum TKA biomarker, and this is outside breast cancer. And then also provide you with an update on our collaborations in the pipeline. That is both collaborations we have the on the lab partnership side, both U.
S. And EU and also on the pharma collaborations. So let's dive into the first topic. And this is really in regard to where to go next with our TKA biomarker outside breast cancer. And to really decide or make that decision, we made a thorough analysis at Biowica.
And we use the 4 guiding parameters you see here to the left, TKA Clinical Utility Therapeutic Fit and Market Potential and Competition as those parameters that So if we start by number 1, the clinical utility. It is pretty obvious that if you want to pursue an indication with your biomarker, There needs to be a clinical unmet need, an unmet need for the patient and also an unmet need that can actually be remedied or helped by introducing our TKA biomarker. So that's number one parameter, very important. Secondly, we also look for indications that have a therapeutic fit to our biomarker. And I guess during the day here, you have heard about our biomarker measuring proliferation of tumor cells.
And therefore, it's only natural to look for indications where you have therapies actually targeting this proliferation. So we look for those kind of indications, target therapies, anti proliferative target therapies, I should say. And we actually also try to avoid indications that are typically treated with cytotoxic treatments. And that is because cytotoxic treatments are, I'd say, less innovative. And also, they are more focusing on killing tumor cells, whereas we are actually focusing on treatments that are anti proliferative.
So very different strategy, you could say. Then also, of course, market potential. We are a company and there needs to be a market potential within the indication we pursue. So a testing potential is something that is requested, But also that there is a clear health economic benefit. You've heard both Amy and Robert talk about With imageostatic breast cancer, we have, avoidance of futile therapy and reduction in imaging.
And that actually has a great Fantastic impact on the HD benefits. And same goes for looking for new indications. There needs to be a health economic benefit the So we looked at the strength of the competition within the individual indications. We looked at the launch status of these competitors and also their thinking of pricing within that field. So that's the parameters we went through.
And the first disease or indication that actually passed our criteria here is metastatic malignant melanoma. As you can see far to the right on the slide, we have green marks there. And that just means that, yeah, this indication passed our criteria. So start by clinical utility. Metastatic malignant melanoma is a very aggressive disease.
And because of that, it is important for the patient that you actually get that patient on the right treatment right from the beginning. So you need a biomarker that can actually at baseline, predict if the patient is going to respond to the therapy. And secondly, when the patient is on the treatment, it is also very important that, as Amy explained, you have a biomarker that can measure if that So aggressive disease and therefore, And need for this kind of a predictive biomarker and a monitoring biomarker is pronounced within malignant melanoma. So a good fit there. Theapeutic wise, actually, within melanomas, There's really no use of cytotoxic treatment, chemo treatment, because they're not chemosensitive.
That was also a perfect match, you could say. We were not looking for the cytotoxic treatments. We are more looking for the targeted therapies, the immuno oncology therapies, And this is exactly what you find within metastatic malignant melanoma. And we continued on to the market potential. And we looked into market potentials initially for U.
S, EU Big 5 and Nordics plus Japan. And we do have a significant market potential, testing potential here. We actually assumed same frequency of testing as we have for metastatic cancer. And I'll come back to the assumptions we made on the But there seems to be a really good market potential. Health economic Also really important here and the malignant melanomas, there are big spending within therapy here because of the very expensive drugs you have.
So 85% almost of the cost cares that goes into malignant melanoma is due to treatment. And on a monthly basis, a patient would actually require a payment of approximately USD 23 to USD 36 $1,000,000 per month. And that is really depending on whether you are in U. S. Or you are in Europe.
It's less expensive in Europe. So again, market potential and AG benefits are obvious within the malignant melanoma indication. Competition wise, we are actually also in a really, really good spot. Because currently, What you use as a monitoring tool within malignant melanoma is what is called immune related adverse events. And that is these patches of white skin you see on patients, And that is due to the therapeutics actually killing the pigment cells and therefore you get these white patches.
So that is one way of actually understanding if your treatment is working, but you also look at a different or another biomarker called LDH And you look for actually that biomarker to decrease and you combine that with actually a profile of T cells. So as you can hear, pretty complicated. It would be much easier just to use TKA as a monitoring device. So all over here, malignant melanoma, we are in a really good spot and that's the first indication we want to pursue with our TK biomarker. And where are we then currently?
You might have seen from our press release And you might also, from the ASCO meeting earlier this week here, have seen some of the abstracts released. And we have now undertaken the first study with success together with Karlinsky Institute and Karlinsky University Hospital. And we actually achieved some very promising results. It shows that TKA It's a very strong baseline biomarker to predict response of these immune checkpoint inhibitors or IO So if you are low on TKA or if you are expressing TKA just at a low level, Then you have a significant higher response to that kind of treatment and your progression free survival and overall survival It's also significantly better if you are TKA low. So a very strong tool TKA in predicting response to IO treatment.
So now we have the abstract out there in public from ASCO, and we also have a manuscript submitted to peer reviewed journal that is obviously done by Karl Inske Institute. So our conclusion right now on the metastatic malignant melanoma indication is that we have a proof of concept, meaning Our assay works from a technical point of view and we have also established clinical utility. So the same way as we did for the metastatic malignant melanoma indication, we also dived into prostate cancer And for prostate cancer, we have actually now Locked ourselves into that subgroup, which is called castration resistant prostate cancer. And that is a disease or a cancer that treatment wise actually have a lot of biological similarities to For the non small cell lung cancer sorry, for the lung cancer indication, we have Decided on the non small cell lung cancer subgroup. And even further there, we have actually said our biomarker TKA is perfectly fitted for the advanced stage within non small cell lung cancer.
And actually, even further, we are focusing on the part of patients that are treated with targeted therapies and immune checkpoint inhibitors, because now we have the results from the Malignant melanoma study. So what I show here on this slide is, again, the market potential for all these metastatic medigal melanoma, castration resistant prostate cancer and non small cell lung cancer and divided into U. S, EU Big SPY plus Nordics and Japan. And also listed here are some of the assumptions that we put into these calculations. As I mentioned earlier on, it's the same test frequency as we use for metastatic breast cancer.
When we Calculate new arrivals, I mean, new patients to be tested. Robert also mentioned That term in his calculations, for these indications, we used 5 year survival rates And of course, the maturity rates. Pricing wise, we have also built into this estimate here that For Europe, it's only 50% of the U. S. Price.
And for Japan, it's 75% of the U. S. Price. And then further on, we also know that in EU and Japan, well, probably mainly in EU and that's the calculations we've made. The targeted treatments and IO treatments are less established than in U.
S. So that is what goes into the overall target or total market potential, which is shown here. Now switching gear or switching topic, at least. I'll give you an overview of where we are in our discussions and negotiations with our lab partners. This is a summary slide and really just to show in colors or color coded where we are.
And you can see we are in signing with some important partners, and then we have discussions ongoing with other partners. We want to establish collaborations with lab partners for two reasons. Number 1 is, obviously, the commercial setting where we want to support our product launch. And then secondly, we also want to establish collaborations with pharma where we can do CKA Research Shoes Only Testing, and that is to support our scientific collaborators, but certainly also to support our pharma collaborations. And we want to do it both for U.
S. And for EU. As you can see, for U. S, we are in signing process on a lab for research use only testing. And thinking here is that it will expand into a Commercial Agreement as well.
Same goes for Europe. As I said, One of the reasons for entering into these partnerships is that we want to enable pharma collaborations. And that is where I want to go next. So I want to give you a short update on where we are with our pharma And this is, of course, an area where we have the possibility of expanding our business, to monitor those drugs or to predict if they are effective. These are the so called companion diagnostics.
If you look at the slide here, we know from our clinical data that our assay can do both prediction, prognosis and also monitoring. Our focus with regard to pharma is, of course, again, those pharma companies developing drugs that inhibit cell cycle, the cell cycle and thereby inhibit cell proliferation. Pharma focus is primarily on predicting response to their drug or monitoring response to their drug. And if we, at the same time, look at the competition, we know that within prediction, there's a lot of competition. Whereas if it comes to monitoring the test a monitoring test to monitor the effect of the treatment, It's still imaging that is ruling and less competition.
So that is why we have picked a monitoring testing as the playing field of ours. Instead of calling a companion diagnostic, we call it a monitoring diagnostic. And we really have a 2 tracked strategy within our monitoring diagnostic together with Pharma. Track number 1 is really where we are building trust at Pharma. It's both a trust in the TKA technology, but it's also our building a trust in Ad Pharma in our way of dealing with pharma, being professionally and diligently actually make sure that we execute according to the plan we establish together the And this track number 1 is where we are currently, and that is also the track that is Over the last 6, 7 months has really picked up momentum.
So we now have 4, 5 project activities together with Pharma in this track. So it's more preclinical and Phase 1 activities with Pharma. But it's strongly picking up, as I said. And this track is actually what allows us to move into what we call track number 2, which is really developing companion diagnostics or monitoring diagnostics Together With Pharma. And this track number 2 is Something we foresee will happen within the next one and a half years' time, potentially with one of the partners with whom we are now And this track is then, of course, about really developing, registering and commercializing these companion diagnostics Together with Pharma.
And the beauty about this Track 2 is that it's actually done according to a business model, which is shown on the slide here. I know it's a very busy slide, so let's take it step by step. On the left side on the slide is really the business model. And it really shows how it works together with pharma. And it's about pharma really paying for having this companion diagnostic test developed.
And why would they do that? And this is really because it gives them an opportunity to have a differentiator on their drug because by having a companion diagnostic that will assure a more safe use of their drug. They can't differentiate themselves from competitors. So what is shown here on the left is On the yellow bar is really that we undertake the development for pharma through a FIFA service agreement. So we are paid on an hourly basis to develop the companion diagnostic.
Then afterwards, the companion diagnostic, Together with the drug or alongside the drug is released to the market and Biowike will get to own that product And also to own the revenue coming from that product. So this is, of course, this is track A and B shown here on the left. And that is, of course, very attractive because you get a the to actually be paid for your development and actually also launch the product to the market. What I also show here on the green arrow going back into the business is what I call a positive feedback loop. And that is because When you increase the number of products you put on the market as a company, Then those products will go into more and more laboratories and we will have our name more and more established in many laboratories.
And that will typically also lead to that our core business products will find its way or find their way into these labs. So that's the positive feedback loop into the core business, you could say, based on the companion diagnostic products. The On the left sorry, on the right side of the slide, more details on the revenue potentials From each of the tracks I mentioned early on strategy wise. So Track 1, as I said, it's the early collaborations with pharma. It is activities mainly focusing on Phase 1 and preclinical.
It's less FIFA service revenue. I think you have seen lately, Perhaps if you look into our financials that we have sold quite a few kits and that is now exactly coming From these collaborations. Less revenue, but it's certainly not insignificant revenue that we receive through this Track 1 collaborations. And then the real upside is, of course, Track 2, when you move into a true development registration and commercialization of a companion diagnostic. And there are some numbers shown here on the potentials of Releasing that kind of products, I should say, from a FIFA service perspective, these projects could be between 17,000, 20000 hours also paid to a certain hourly rate.
So also the a decent fee for service revenue coming in there. And that is leads to a yearly revenue potential per CDX as also provided on the slide here. Yes, so I think overall, We're looking into a bright future with our business development activities And coming activities, new indications. And by that, over to you, Anders.
Thank you, Henrik. I don't know if this is the best way to describe the bright future looking for us ahead. But I'll just summarize what Henrik and Robert just talked about. Although our focus still is metastatic breast cancer monitoring prostatic breast cancer in U. S.
And the launch of the product for that use. We have actually initiated a lot of activities to widen use over time. And so we the white marked arrows are the one where we'll be making investments. And we're making an investment now and we've done for quite some time to launch the product. And really soon now, we expect in the quarter 3, the regulatory approval or clearance in U.
S. That will be the starting point to build revenues to 3 years after launch reach 50% on market potential. And we expect over time peak sales of about 50% of the market potential. And as we also told you, we are looking already now into the European countries, focusing on the top 5 in the Nordic countries. And before end of year, we are expecting to be able to launch in the 1st European countries and then widen use within that region as well.
And the 3rd focus area is the Japanese market, where we together with a partner will have to expand our regulatory clearance. And so that will be an additional activity for Japan. But in that we can also build on the strong data set that we have and the collaborations within the breast cancer area. And the next area for expansion within the breast cancer area is locally advanced, where we see that the treatments being used within the metastatic setting is expanding into the locally advanced area as well. And that will require regulatory new regulatory process, a supplementary to the current 510 intended use.
But also there, we can benefit from the fact that we included in these type of in the locally advanced setting already and have a strong network of collaborators that can help us generate the data required for that regulatory process. And also being having launched a product on these three markets from metastatic breast cancer, we have established sales channel's collaborating partners and commercial agreements with labs and so on. So that launch process will be a lot smoother and simpler than the initial launch within breast cancer. And as Henrik talked about. We are looking into new indications outside of the breast cancer area.
First of all, metastatic melanoma. We have proof of concept that's being currently presented on ASCO. And we are you can also expect to see proof of concept data within the other areas, prostate cancer and non small cell lung cancer that was mentioned by Henrik. And we're looking also to these 3 target markets for these applications also initially. Talking about market potential, we previously said that the metastatic breast cancer area or monitoring within metastatic breast cancer it's USD 400,000,000 to USD 700,000,000 per year for these markets.
And locally advanced will add another 30% to 40 asset to that market potential. And if you look at the additional indication that is also adding a big market potential within these three areas. And the last one, companion diagnostics, where we can leverage the fact that we already have pharma as customers using our assay for developing new therapist within the cancer areas. A natural step is to develop those collaborations further and move into collaboration project, which will be a very attractive way business model wise for us to develop new products that will expand the use even further as we would get paid from day 1 of the collaboration. But of course, the real potential is the terminal of the potential of the new therapy.
But when the therapy reaches the market, also as a diagnostic company providing complementary diagnostic, would benefit from that as well and will drive sales of the diagnostic product. So yes, a lot going on, although the focus is still on the U. S. Launch, but we have initiated and have activities ongoing in several areas currently. And to sum it up, we have a product with a great potential that addresses an unmet need for improved monitoring in metastatic cancer in general and metastatic breast cancer specifically.
And the collaborations with leading key opinion leaders and academic centers has resulted in strong set of clinical data proving the value for the product. And that is the foundation, the basis for all our commercialization activities. And right now, we are in a very exciting moment where we are in the later stage of the discussion with the FDA. We expect a clearance during quarter 3 this year, which will be the starting point for our U. S.
Launch. And before end of the year, we expect also to have our first reimbursement on the U. S. Market and also the launch of the product in one of the European and Nordic countries as well. So there's a lot of milestones to look out for the remaining part of 2021.
Thank you very much for listening so far, but it's not over yet Because we will open up for a Q and A session. And for that, shalot, please, and Henrik. Thank you, Anders.
And Henrik, please. Team. It's a great team.
It's a lot of great people contributing and we've also been able to mobilize and work with some fantastic oncologists that also are helping us in our development. And of course, we all do it because it we can I think a strong motto, in fact, for all of us is that the fact that we can contribute to better outcome for patients?
I'll start by saying to you all that if you have any questions, please post them at irbiovica. The And the milestones that you put up, starting with FDA clearance. Yes. You said in January, Already in January that you expect Q3. Are you more or less certain now that you will reach clearance in Q3?
And also we had a question from Redeye on this FDA. Are you in the interactive review stage?
All right. Yes, I would say we're more certain because the process as the FDA also set the expectations wouldn't follow their normal process. So initially, we were in discussion, then there was pause for a while. And of course, we got a little bit worried. But now we're back and we're having a good discussion I think we understand what the FDA is looking for and we will be able to come back with the results.
So yes, with that in mind, I would say that I'm more confident now than when the process was kind of halted, yes.
More confident now. And now we actually have yet another question from red eye on this FDA approval. When do you expect to be in a position when advanced breast cancer is covered by the FDA approval? 1 year after the Initial approval? Do you dare say anything about that?
Locally advanced? Yes. Yes. Now we have to come back with detailed sidelines on that. We haven't disclosed milestone for that, but we are already included in clinical trials within local advanced as well.
So, yes.
Okay. And previously, you've said that you'll sign a partner in connection with FDA clearance. Now Henrik is saying you're already In discussions when it comes to the clinical use, so to speak. Sorry. Yeah.
So could you just Elaborate on this. When do you expect to be out in the labs?
Yes. So what we're doing is, we're obviously discussing with laboratories in primarily in U. S. Initially, but also preparing for Europe. And discussions are research use only.
The These are the agreements we have in signing now. But then also expanding the discussions with these partners on actually having them carry our assay as an IVD test, commercial IVD testing. So that's where we are currently with our discussions with pharma sorry, with lab partners.
And I think that the market has thought that these Being as an IVD test, that would be when you get the FDA clearance.
Yes.
How fast can that happen before or after FDA clearance?
We like an efficient process as possible. But by doing the way Henrik is describing, we can actually start doing the validation already before the clearance, which, of course, takes that away from the critical path. I can't promise a date, but it will be that way we have an efficient process and we can gain time market.
We have a question from ABG as well. Have you started to establish any best practice or protocol On for how other often patients should be monitored.
Yes. I think, Robert, you covered that. Briefly want to elaborate a little bit about that.
So thanks, Anders. What we've done on this is we've consulted with oncologists, both looking at their clinical trials and looking at how their practice actually is. And as I indicated, we've made some small updates to this over the last 12 months. Because 12 months ago, we did not talk about the addition of this test at 2 weeks after the start of treatment. So their expectation is, at baseline, 2 weeks after the start of treatment, Monthly thereafter during the early part of treatment out until 6 months.
At that point, they've got a pretty good sense of who's a good prognosis patient where they can take half a step back and they expect to reduce frequency to every 3 months. So that's the best advice on how this would actually be done in clinical practice that we've got at the moment based on the studies that we've done.
And there is a follow-up question on this. Could you go into more detail in what sort of things you're looking for in Partnership. Is that for you, Henrik, perhaps?
Business Development, Henrik.
Yes. We are obviously, we're discussing several things. Of the coverage because we need to have a certain coverage for our test. And it's not going to be only one lab, it's going to be several labs, obviously. But I think coverage and then terms on pricing, I guess.
I'll continue with the ABG questions. How does How does the dividend predictive difference in progression free survival compare with other biomarkers? Predictive The predictive difference in progression free survival. So is there a difference between yours and other biomarkers When you compare them?
I think in general, it's not that often you see diagnostic companies come out with biomarkers and progression survival, overall survival because they typically don't undertake that kind of studies for a biomarker. We had a chance presented by Luka because we are tightly connected to therapeutics and the monitoring of therapeutics. I guess that's why we have the PFS and OS And specificity, it's a different story, I would say.
Yes. We have some questions also from Pareto. Could you elaborate on your product launch readiness?
All right. And by product launch readiness SME.
Have you already started some additional marketing efforts outside KOL Networks? How are you building up the sales force in the U. S?
Yes. Okay. That's one aspect. Another aspect is securing the production process and the supply I can start with that. And or you can start, Robert, with the sales SVP of the company, and I could complement with the supply.
Is that okay?
So a couple of different things that I'll touch on. One is that we are in the midst of some recruitment activities at the moment. And as those are completed and we add new faces to the organization, we can communicate on that. 2nd, we've gotten much deeper in our understanding of the reimbursement environment and are ready for the challenges and complexities of that in the U. S.
The budget impact model is one element. I described the results of that. The other is that we also did a payer advisory board to get their reactions on what is and To be honest, what is not reasonable from their perspective, so that we know what we're heading into when we launch this And do not face a situation where a large number of the claims for reimbursement are denied. So we're moving forward step by step in several different areas. Anders?
Yes. That's good. So reaching out to oncologists is important. We have talked a lot about our clinical development program. Reaching out to payers is important and the Payer Advisory Board and the reimbursement strategy and all that work is important.
I would say another group which is important is reaching out to patients. And we have also similar activities with the patient organization and patient advisory groups coming up very soon. So yes, we're preparing to get creative awareness for the product. And then maybe the supply side of things. If we create demand, we need to be able to meet the supply.
So in parallel with developing everything for the 510 clearance process, the applications, all the data that's required for that. We also have worked with our production process, securing both quality and being able to produce volumes in parallel. So that kind of goes hand in hand with the product development. We also done a production process development, yes. So we have invested time and effort in that as well.
And that's based in our facilities in Uppsala.
So you are more sure than before On FDA clearance at the end of Q3, you seem to be very prepared for market launch. And you know what you have to do. Have you put up any goals for the coming year where you think you will be in
In U. S, Robert, maybe you can start, maybe I can complement with Europe.
So I think the commercial organization that I described on my slides should be in place during the course of the next 12 months As we add people to the organization, I think you'll also see a number of early agreements with payers. Within the U. S, there's some pretty clear distribution of payers from those who are early adopters, quick to Bring in new tests, enter into risk sharing agreements, and those at the other end of the spectrum who typically choose to follow. I think we should have some of those early adopter arrangements in place in the near term. And I also think, as Henrik indicated, we should Have the necessary lab arrangements in place within the next comfortably within the next 12 months as well.
And Europe, we're also progressing, although we're not as hasn't progressed as far yet as in U. S. But we have a Commercial Director now working on the first agreement by end of this year and a go to market plan, which we will communicate later this year, which we plan to communicate on our Q2 report in December to be specific. So we will come back with a more detailed plan for Europe.
It sounds like you have a good plan for the U. S, for Europe, but we have a couple of questions on how well funded are you Yes. To do all this.
So we are well funded is a really short answer. And the reason for that is that we did a successful capital injection process last year, where we in end of August, we raised SEK 148,000,000 and also we expanded our shareholder getting some more institutional investors in to complement the already strong shareholder list. So and we at the time also had cash at hand. So we are we went into this process with a really strong cash situation, which is, of course, very good now when we are investing in the go to market activities.
And we have some outstanding questions on your studies. So there is one from Red Eye. How many prospective studies have been completed? How many are ongoing? And when can we expect these to finalize?
I think we have 1 completed prospective study. And we have 2 ongoing and we have a Couple in pipeline.
Just like Amy talked a little bit about. Yes. Amy covered had a slide on this actually and Luca presenter also. So I think you're right. And the completed one is the Pithya trial that Luca had slides on.
And it's completely it's been presented. And what he said, it's about to be submitted anytime soon in his presentation. And then you can expect a couple of months up to 6 months before publication. So that's the process normally.
And then we have a question. I guess you are already approved in Europe, but the question is, when will dividend be submitted for the European Medicines Agency? When is it expected to have it approved by EMEA? And are there any additional approvals necessary for commercialization?
CER. That's a good question because we already have CE Marking. But we have further developed our product, as I said briefly in my presentation and it's the improved version that we're going to the FDA. And we will also go to the EMA, the European Association. And first, do our CE Marking on the IVDD, it's a bit technical here, but they are changing their standard.
So we'll do it with the current standard before launch in Europe by end of year. And then we are also well prepared for the coming standard, which will be applicable mid next year, you can say. So we are actually doing quite a lot of regulatory work for Europe as well. The good thing is by doing this U. S.
First, we are able to reuse a lot of the assets and the work. If we would have done it the other way around, that would have been much, much more difficult as the U. S. FDA, requires clinical validation for this kind of product, and it has to be based on U. S.
Patients. So that's why it's important to do it that way. I have a U. S. Trial for clinical validation.
Once again, I just want to say if you have any more questions, we've received a lot of questions. I hope that we have answered the questions you have. Ir@bywijk.com. If you want to ask any more, I'll get them in the computer and ask them for you. I had a question on you are on the Eliza platform, and it's not the most modern.
Do you have any comments on that?
Yes, we can comment on that, Henrik. Do you want to comment on
that? I
know that this is an area you know well.
Yes. I mean, it might not be the most sexy and newest invention, the ELISA platform, But it's actually a very, very established platform around the world in every laboratory. So if you really want to enter the market with a new bio I think ELISA is actually not a bad choice because you will be able to access all laboratories.
Good. I think actually we have covered the questions more or less that we have received in one way or the other, although we haven't I'll leave the floor for you, Anders, if you have any concluding remarks, but you've said it all.
Now I'm grateful for I've seen the number of participants. I'm grateful for the interest. And I thank you all for participating, I think to my colleagues and to Doctor. Malorny. And I'm sure that with our very exciting product, Divitum, that can create a lot of value both for cancer patients S and Health Care Providers.
I'm sure also that will translate into shareholder value for our shareholders. So Thank you very much, and we're looking back to update you on your coming progress. Thank you.