Hello everyone, welcome to the Biovica Capital Market Day of 2021. My name is An ders Rylander. I am the CEO of Biovica. 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 Axholmen, which led to that I eventually came into contact with Biovica as an investor. I was attracted by the great potential, both human and commercial, and the fact that we, with our product, can be beneficial for cancer patients on treatment and also for payers and healthcare providers. We'll get more into detail int o that today. Now today I'm both the CEO and the main shareholder of the company. Talking about the agenda for today, we have two and a half hours. We'll go through, first of all, a company overview, which I will do.
Then Dr. Malorni from Prato Hospital will take us through the oncologist p erspective, as he has great experience from working with the test and clinical trials. Following that Charlotte Gylche will facilitate a Q&A before we go over to Amy Williams, our scientific director in U.S., and will be talking about the clinical utility for DiviTum. She will be followed by our Senior Vice President for marketing in U.S., Robert Dann, who will talk about our go-to-market plan for our first application metastatic breast cancer on the U.S. market. Senior Vice President Henrik Winther, heading up business development, clinical development, will talk about how we intend to expand outside our initial area. After a short summary from me, we will open up for questions for the Q&A session, which will be facilitated by Charlotte Gylche.
You can also submit your questions, so there's a form on the screen that you can use and submit questions for the Q&A session. 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. 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. It also creates a different problem of complexity, as all patients does not respond to all treatments. 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.
Here is 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. How does that solution look like, and what is it? Well, the product is called DiviTum, stands for dividing tumor, and that is an indication of what we do. We measure cell proliferation, and as you know, the way cancer grows is through cell proliferation. We are able to measure this by measuring an enzyme which is prevalent in the patient's blood. From a blood sample combined with a product that is implemented on a standard platform for easy rollout on the clinical labs out there, we are 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 aggr essive the disease is, a prognostic value.
We're measuring cell proliferation, what eventually will become an increase in volume. We've 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 two weeks after start of treatment can provide feedback if the patient is responding, if their levels are being significantly reduced. Currently, it requires three to four months before you can follow up on image using image diagnostics. Talking about other diagnostic technologies within the monitoring field, imaging is a standard method, as I said, and it requires three to four months before you're able to follow up.
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 complementary tool to imaging within the field of monitoring. The same goes for biopsies, where you take a needle and you take a sample of the tumor and you analyze that, and you can do a lot of things with that. You can do proliferation marking, just like DiviTum, and you can do gene sequences, look for mutations and so on. Biopsies is a great tool to, for instance, predictably decide which treatment to use. It has its shortcomings within monitoring. When you take serial testing, it's not used currently that way. For biopsies, 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 CA 15-3, but it's not been 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. DiviTum has been compared once in a clinical trial from Karolinska, where we outperformed CA 15-3. There are also other new technologies. CTCs is one example. I would say newer, because that has been around for quite some time now and has established itself within areas more to determine risk for recurrence and progression rather than monitoring. It's an earlier phase, you could say, of the treatment process. Not a direct competitor either. That also goes for the newest technology of these mentioned, that's the ctDNAs.
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. At the same time, it has shortcomings, that it requires a lot of blood and also is quite complex and costly. The focus areas has more been into more predictive applications, and we don't see it as being used in monitoring either. We also see DiviTum as a great complement to CTCs and ctDNAs rather than competing products. 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 oncologists within the field, like Dr. Malorni, 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. The majority of these is within our focus area, breast cancer. We also have proof of concept data within other important cancer areas like the gastrointestinal and lung cancer area, for example. If you should summarize the results, you could say in metastatic breast cancer where we have had access to several samples, have been able to evaluate those. We've been able to monitor the treatment process and provide quick feedback on treatment efficiency.
In both early local cancer and metastatic cancer, we've shown that we can be prognostic before start of treatment, assessing risk for recurrence in the local setting and both progression and survival in the metastatic setting. These results are consistent over several trials. 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 third trial. Shortly thereafter, we started our collaboration with the Prato Hospital and Dr. Malorni and his team, and we have now done several collaborations together with that team. We've also done a prospective trial in Euro pe with the big IBCSG group, which covers several countries in Europe.
In U.S., we also have several collaborations with Washington University, Mayo Clinic, Baylor College, Johns Hopkins, et cetera, in different clinical trials, primarily within breast cancer. Going into the breast cancer area, this slide is a breakdown of the results so far. As you can see, we have from early phase all the way to the metastatic setting, but our focus area is the metastatic setting. That's where we see an unmet need that we can meet, like I talked about previously. Now we're building a very solid set of documentation, which will be the foundation for the entire commercialization process. You see the blue ones here are the ones that have 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.
The white ones are the ongoing trials that we are doing to strengthen our data and evidence of the potential and the value of the product. The reason we do that is to be able to bring the product to the market to clinical use and uptake. 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. 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.
As we are looking to launch to enter the U.S. market, the 510(k) process by the FDA is our focus, and I'll get back to where we are in that process. Regulatory approval is not enough. You need to make sure that this becomes a part of the guidelines, the standard practice to use the product, and also that you get paid for the product. The clinical data that we are generating is not only for regulatory use, it's also for guidelines reimbursement and also to 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. 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, that's of course really important to us. We have submitted our application already in third quarter 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. 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. We are very grateful for that. 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 timeline. We see a slower process, but it still is progressing well. That's why we keep our milestone that we expect to see a clearance of the product in the third quarter this year. I talked about the U.S. market being the first one we intend to launch the product. We have also estimated the market potential 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 third step. 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, and the treatment guidelines and so on are very similar.
Going back to the market potential, those figures you see here on the different markets is based on market research that we've done, where we have interviewed payers for the value and the price sensitivity, and the key opinion leaders, oncologists for how they would use the product in the clinic, combined with the number of patients living with the disease. 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. In total, we estimate the total market potential for the metastatic breast cancer monitoring market to $400 million-$700 million/ year, we should say. Yeah.
To be able to execute on this plan, of course, you need to have a strong team with great experience from doing this previously. So that we have. This is our management team, where we have different functions with people that have done this before. We have an experienced team which just recently have been strengthened with Helle Fisker, which is the commercial director, started a couple of months ago. Also in the board of directors, we have people with great experience doing similar projects, both within diagnostics and oncology pharma. That contributes greatly to the development of the company. Lars Holmqvist being the chairman, has a history at Dako, where the CEO and was part of the transaction when Agilent acquired Dako in a successful transaction.
Since then, he's been part of several larger diagnostics and pharma companies, for instance, like Vitrolife and now Biovica. All of the board of directors have holdings in Biovica 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 Dr. Luca Malorni at the Prato Hospital in Italy. Luca, please take us through your slides and maybe a short introduction of yourself before you start.
Thank you very much for this invitation. Hi, everyone. Just a brief introduction. I am Luca Malorni. I am the director of the Translational Research Lab here at Hospital of Prato. I'm a medical oncologist. I am very much interested in translational research in oncology, and in particular in biomarker development for breast cancer in particular. For that particular breast cancer that expresses hormone receptors, which is, of course, as you may know, the most common subtype of breast cancer. Why I'm here today, I think Anders made a great introduction to my slides, because we have done quite a lot of work in collaboration with Biovica in the past few years, since the very beginning of the use of this DiviTum assay for research purposes.
I'd like to start this conversation with you about our experience with this DiviTum test by starting with our very first publication we did back in 2018. I will go 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. The concepts that we developed in this paper were then taken for other studies, and I will show you what progress we have done in the field. If I can have the next slide, please. The concept, as Anders was just saying a few minutes before, is that this assay measures tumor proliferation. The beauty of this as say is that it's very flexible, and you can, of course, for clinical purposes, you can do it on the blood of the patient.
Pre-clinically, so in the lab, you can even use it in cellular models. This is what we did to begin with, because we wanted to have a proof of concept that breast cancer cells that respond to treatment actually have a response also, a reduction also in this biomarker. 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. 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. The endocrine-resistant cell line, which is depicted here in red, where you do not see an effect of the endocrine treatment.
You do not expect anything to happen when you treat with endocrine therapy. If I can have the next one, please. Next slide, please. 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. This is done basically by counting cells. That's the top panel. On the lower panel, we have DiviTum. You see that those two endocrine-sensitive cell lines, when treated with endocrine therapy, as expected, they both respond in the top panel. You see a reduction in the number of cells, but you also see a reduction in DiviTum. DiviTum is 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. You see a perfect reflection in DiviTum of what is the behavior of the cells during treatment. The interesting thing is that while you need many days to observe these changes in the upper panel, because you see we have to observe cells up to six to nine days to see a decrease in cell number. Actually, with DiviTum, you just need a couple of days, because by day two, 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.
You have an anticipation of the phenotype, so of the behavior, of the sensitivity or resistance to the cell, compared to what you will do with usual techniques. 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. Next, please. We observed this in cellular models, so in cell lines. 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 patient won't be responding to endocrine therapy. You see, we collected a small cohort of about 30 patients.
If I can have the next one, please. Yes, this one. Exactly, please. The first take from this is that, as you can see from the numbers, but it's just easier if I comment on that, we collected baseline samples, so before starting treatment, samples from same patients after one 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 disease progression. As you can see from the median levels of DiviTum, which is written in this table, the starting point was quite high, 122, but then only after a month of treatment, it dropped significantly to 36. Then when the patients were progressing, it increased again to 330.
The take from this first data was that the activity of TK1, DiviTum output, is reduced by the treatment, and that this increases again at disease progression. It goes very well with the concept that when tumor is responding, it goes down, and when the tumor comes back, the levels come up again. If I can have the next slide. This is seen very well here. You see that this is what we call a spaghetti plot. These are patients, individual patients, across two different time points, and this is in particular the early time points of one month after treatment, the starting point and the first month of treatment. You see that most of the patients have a spaghetti that goes down, which means that they were dropping their DiviTum levels.
You also observe that there are some, the blue ones, who actually increase. If you look at the outcome of these patients, the interesting observation was that most of the patients with an increase during that first month of treatment were patients who actually were not responding to the therapy. 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 DiviTum after only one month of treatment had a very good outcome because they had a median progression-free survival, which is the metrics that we use in the clinic to understand for how long the patient benefits from treatment, which is quite long. It's 14 months. This is only using classical hormonal therapy.
While those patients who had in that first month of therapy an increase in DiviTum, they had a very short progression survival probability of only about four months. You see, this is a substantial difference. This was, of course, statistically significant. The take, if I can have the next one, please, from this is that not only we observe early changes in responding patients, but that this early response is very clinically informative because only after one month of therapy, in this case, we can have long-term information on the outcome of patients. Next one, please. This is also interesting because not only the difference between the baseline and one month, so the change was informative, but also the actual baseline level.
If we stratify patients for the baseline, before starting treatment DiviTum levels, we see that those with high levels have a worse outcome as compared to those with the lowest level. This is also important because we are always looking in the clinic for prognostic markers or those marker 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. Actually, in this small cohort, we saw a very good prognostic value for baseline also DiviTum levels. Next one, please. This was a first and initial experience, and I think it was very positive.
All the answers we wanted to have were there, but of course, we needed, and the scientific community also needed, larger sample size, more patients, and different studies to actually believe that what we were saying in a smaller study was actually replicated. 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 to this phase III trial, it was called EFECT. This is a trial that was comparing two different kinds of hormonal therapy for metastatic disease. 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. Even in this case, we had 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 DiviTum levels were a very good prognostic indicator, but also the change between the baseline and the three months in this case, because this was the earliest time point that was collected in the study after baseline. It's not that early as the one month we have seen in the previous one, but this is the best we could get. The change between baseline and three months was also very informative. Those patients who had a decrease in those three months in DiviTum did much better than those patients that actually had a stable or an increased DiviTum across the first three months of treatment. Next, please.
The final take is very easy, that the study fully confirmed what we expected in the smallest previous study. Next one, please. We moved to a different scenario. By the time we had done this first experience, CDK4/6 inhibitors, a new class of drugs, had become the standard of treatment. Now we don't treat patients any longer with single agent hormonal therapy, but we use hormonal therapy in combination with this new class of agents. We thought that DiviTum was a good biomarker also in this setting. This is why we applied DiviTum 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. We made a sub-study in this clinical trial, it's called TREND, with DiviTum. Next, please.
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 of acquired resistance to this new class of drugs. Just to make a long story short, we realized that Thymidine Kinase 1, which is the gene that encodes for thymidine kinase, that is the target of DiviTum assay, is one of the top differentially expressed genes between sensitive and resistant models. This means that when the cells become resistant to this new class of drug, they have an increase in TK1 levels. We argued that the increase in TK1 levels would also reflect in an increase in DiviTum activity. Next one, please.
We went back to the models that I showed you in the first study, and we compared what happens in sensitive cell lines to CDK4/6 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 the drug and you do not see any change in DiviTum levels, while you do see an early response of DiviTum in responding samples. This convinced us that not only in the hormonal therapy alone, but also in the hormonal therapy plus CDK4/6 inhibitors, the new standard of therapy, DiviTum was going to be an effective biomarker. This is why, next slide, please. Next one, please. We applied DiviTum to samples taken in this study, which is called TREND, as I told you.
Next, please. Even in this case, we showed that the dynamic change, so the change between baseline and in this case, also a month after initiating treatment, was very clinically informative because those patients who actually had an increase of TK activity during this first month of therapy, had a very bad outcome. You can see from this black curve that these patients really do not benefit from the treatment, while those patients who had a decrease in DiviTum during this month of therapy had a better outcome. This told us that what we had seen in the previous studies in hormonal therapy alone did also apply to the new standard of therapy with CDK4/6 inhibitors. Next one, please. Next one, please. 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. They are two important international cooperative group for the study of breast cancer. This study is called PYTHIA, and this phase II biomarker study that was developed with the aim of looking into new biomarkers of sensitivity and resistance to CDK4/6 inhibitor, and in particular to palbociclib, which is one of the first CDK4/6 inhibitor that was marketed a few years back. If I can have the next one, please. Also, in this case, we collected samples across multiple time points. In particular, it was a baseline, like in the other studies. 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 one month.
We also had the day 28, so a month of treatment. We had this intermediate time point of day 15, which we had never observed in the past. As you can see from this spaghetti plot, you see here now more spaghetti because there is more patients. This is a study of 122 patients. 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. This is kind of technical, but this DiviTum assay has a level of detection. We call it limit of detection. Underneath this limit, the test is basically completely negative. It is almost like it is undetectable. It is so low that you have to say that it is undetectable. Okay.
You see that in a lot of patients, after 15 days of treatment, this DiviTum went so much down that it was undetectable because it was below 20. You had somehow a rebound at day 28 of cycle one, so after a week. This is because, and I haven't told you this because this is kind of technical, but the reason why there is this rebound is that the palbociclib, the CDK4/6 inhibitor we're giving to patients in this study, is dosed with a schedule that is three weeks on and one week off. During this day 15 and day 28, there was a week of therapy that probably allowed the cells to start again to proliferate a little bit. Of course, this schedule in the clinic is given for toxicity issues, so we cannot give it differently.
It's very interesting that this assay is so sensitive that it can actually capture also these small differences during such short windows of time. If I can have the next one, please. The question was, we see a reduction at day 15, a small rebound at day 28, but is this clinically informative? 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. This is kind of confirmatory of what we had seen before. 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 seven months.
It's very different in terms of treatment activity. Next, please. What was most striking is the effect at day 15. 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 five months. If you see the blue curve that depicts these patients, you see that, again, around six 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 for quite a long time.
This is not the case for patients who do not have a DiviTum response at day 15. Can I have the next one, please? Day 28 was also very informative. You can still see this very good prognostic role even at day 28. Next one, please. These results that I just shown you were presented at the San Antonio Breast Cancer Symposium last year. We are now in the phase with IBCSG and DI of writing the manuscript. We should be ready for submission very soon. In the meantime, we have continued our experience. There are two relevant next steps, which I want to share with you. One is this BioItaLEE trial. This is a large trial of about 300 patients that are treated with hormonal therapy and a different CDK4/6 inhibitors compared to the one that I just showed you in the previous trial.
This is ribociclib, and this is produced by Novartis. This is a Novartis sponsored trial, but 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 ribociclib and hormonal therapy. This is being implemented prospectively in this trial from the beginning. As you can see from this graphic here, also in this case, we will have baseline, day 15, day 28, first imaging, and then we have disease progression. There's a lot more to learn in this study. We aim here both to confirm our previous data, but also to deepen our understanding on the use of DiviTum also at different time points.
For example, to understand also what happens in those patients who respond at day 15, but then they rebound at day 28. Things that we could not look for in the previous studies because there were few patients, but now with the sample size that is so big, of course, we can do that. The next slide, please. The other study that we are conducting, this is called the TIRESIAS. This is a study that it's an Italian trial that we are running from a year or so. 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 CDK4/6 inhibitors, and DiviTum is one of the main study endpoint.
Also in this case, as you can see, we will extensively collect samples during the treatment with hormonal therapy and CDK4/6 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 the discretion of the treating physician. We will see also the added value of using DiviTum in other treatment contexts after failure of CDK4/6 inhibitors, which are the standard of care, as I told you, in the first line setting. With the next one, which is just acknowledgement, I think I'm done. I'd like to thanks again Biovica for the invitation and you all for your attention. Thank you.
Thank you very much, Dr. Malorni. Those results that you've presented are very impressive. My first question would be, how would you use DiviTum in your clinical practice, in your daily practice, given these fantastic results?
Yeah. Thank you for this question. I think it is very easy, the answer, just because of what I have already just shown. 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 results we have seen in our hands, but also in other study, clearly says that. This is very much in line with the biology of tumors or breast tumors that we know. Proliferation is very important to distinguish aggressive tumors in breast cancer from less aggressive ones. It makes a lot of sense that if you can measure proliferation at any given time point, this is going to give you strong prognostic information. If I could use DiviTum in my daily practice, I would use it as a baseline characterization of the patient.
A patient comes in, I get to know her, I collect the clinical history, the past history, all the prognostic information that I can get from the tumor biopsy, the previous treatment, and so on. I would add also this to the list of things to look for because this gives a very good sense of where the patient sits in terms of prognosis. This, of course, would help in choosing a 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 that this patient is in a low prognostic group. I think the most exciting and most important application for this in the clinic would be the on-treatment evaluation.
The fact that in only two weeks of therapy, you can have inform ation on how the patient will go in the next months, it's very important because currently, we lack this information completely. If we can substitute the baseline evaluation with a number of different clinical information that we can get from the patients, we have nothing that can compare with DiviTum in the clinic to the on-treatment response that we can see. I think we have tested this now, as I showed you, both with hormonal therapy alone and hormonal therapy in combination with CDK4/6 inhibitors. 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, DiviTum would be suitable for monitoring response in most of the treatment that we use in metastatic breast cancer.
Also other treatments which are not endocrine or CDK4/6 inhibitors. 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. I think that if I had a chance to use it in the clinic, for sure, I would do it the baseline and the on-treatment evaluation to understand the prognosis and the response to treatment in that given patient.
It really sounds like DiviTum can be clinically useful, so I'm glad to hear that. You also mentioned that you lack tools today. Aren't there tools like ctDNA today? What is your view on that?
It's true, there are other markers that potentially we can use. However, they're not as versatile as DiviTum 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. Not every patient has enough circulating DNA that can be measured. 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. 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.
For these patients, the only example is the mutations in the PIK3CA genes, which allows you to give a specific drug that is alpelisib, that is the PIK3CA inhibitor. Other than that, there is not an added clinical value in knowing if a patient has a certain mutation or a different one. On top of that, of course, it's not clear whether you can confidently use changes during treatment of ctDNA to understand if the patient is responding or not. In other words, ctDNA is important for precision medicine when you have a target, and in metastatic breast cancer, hormone receptor-positive, HER2 negative, it's one drug only, no more than that. It's very limited potential to monitor disease. 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 a mutation to detect. While with DiviTum, we always had, in all our trials, results for each individual patient. Every patient gets a result for DiviTum, every patient gets a result that is clinically relevant, while the same cannot be said for circulating tumor DNA.
Clinically relevant results. We like that very much. Thank you very much, Dr. Malorni, for being with us today. Good luck with your research. Thank you.
Thank you very much for your invitation.
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 two 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 precision 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 DiviTum 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 two ways that DiviTum can 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 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 two to three months. 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 three 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 three 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 three 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 three 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 fivefold increase as compared to the prior reading. This increase in tumor proliferation activity was detected by DiviTum a full six months before being picked up by an imaging scan. The average lead time between detection of tumor growth by DiviTum 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, o r 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. I've told you about the potential for reducing imaging. Now I will talk about the other key utility for DiviTum, which is to quickly identify when a therapy is not working. Next slide. Predicting which cancer therapy is best for a particular patient is sometimes like having to pick from two 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 two weeks into the journey instead of three to six months. Here's an illustration of how this would look in the clinic. On this slide, you have two 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. One will respond well to a CDK4/6 inhibitor, and the other half is what is called primary resistance, and from day one will continue to grow despite treatment with the drug. This class of drugs, known as CDK4/6 inhibitors, as Dr. Malorni explained, are the standard of care first-line therapies for 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 two years, with some patients having an extended benefit of three years or more. However, not all patients benefit equally from this combination treatment.
About 15%-20% of hormone receptor-positive breast cancer patients will have primary resistance to CDK4/6 inhibition, which means their tumor will not respond at all to the medication and will show progression within three to six months of starting therapy. Right now, on day one, 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 CDK4/6 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 Dr. Malorni, that if you use DiviTum to test for thymidine kinase activity before starting treatment with a CDK4/6 inhibitor, and then again two weeks into treatment, you will see one of two 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 to the baseline TK activity level, and may even potentially rise. Yet it could ta ke six 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 CDK4/6 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 and toxicities 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. 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. To better understand these opportunities to impact and improve patient care, we have a number of ongoing and planned studies which are outlined here.
For monitoring disease stability, we are participating in a 100-patient study at The Christie Hospital in the U.K., as well as several cancer centers in Sweden, which will determine the optimal frequency and timing for DiviTum testing in metastatic breast cancer patients receiving CDK4/6 inhibitor-based therapy. We are also planning two 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 Johns 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 thymidine 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, Amy. 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 has either directly or indirectly focused on cancer care. 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. 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 DiviTum 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.
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 U.S. launch in metastatic breast cancer. Next slide, please. Here's the definition of the population whose needs we're 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 Dr. Malorni indicated, should be suitable for treatment with endocrine-based therapies and post-menopausal. These filters bring the target population to 31,000 new cases arriving each year at this point in care. These 31,000 patients can each receive up to three lines of endocrine-based therapy in a sequence. Median time on treatment for the first therapy, as Amy indicated, is about two years, and it drops to about six months for third-line treatment.
For all the time while the patient is being treated with one of these therapies, DiviTum can be a part of a disease monitoring strategy. Notably, the cost of some therapies used in this sequence exceeds $10,000/ patient per month. That's important when thinking about time spent on a 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 Mrs. Jones, first diagnosed with early breast cancer seven 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. Mrs. 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 Mrs. Jones is apparently one profile of patients and Mrs. Smith is another. But during treatment, these profiles can change. Mrs. Jones' disease can become resistant to treatment, and Mrs. 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 three things, coding, coverage, and payment. 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 DiviTum, 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. We commissioned an external assessment that was recently presented at a major health outcomes conference. I can share the results today.
Top line, inclusion of DiviTum 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 DiviTum. For a new test, at step one, 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 two, there could be a mention in the narrative of a guideline, without changes to the care path.
This will lead to coverage in a greater number of payers. With evidence of clinical utility, step three, 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 four, 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 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. Second, the monitoring pattern probably contains redundancies. 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. There is a usable category for DiviTum tumor markers from day one. This will facilitate payment. As the studies that Amy described are completed, we will aim for a new category in the guidelines that differentiates DiviTum 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, that will come with additional data and evidence and follows very strongly the directions that you heard from Dr. Malorni 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 healthcare costs. The model was created by a team of health economists at the University of Washington Fred Hutchinson Cancer Center. It first examines current costs for care of metastatic breast cancer patients, then introduces DiviTum in two scenarios. 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 one, the clinical consequence of introducing DiviTum into practice is that the frequency of imaging exams is reduced by about 50%. In scenario two, in patients with primary resistance to CDK4/6 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 DiviTum. As health economic outcomes go, this is a very positive result for a new intervention. Keep in mind, most changes simply add cost. 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 U.S. While there are other oncology reference laboratories beyond this list, it is not a large group. 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 lab 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 for how DiviTum adds value to the healthcare ecosystem. The local U.S. team will also take a strong role in further developing the clinical evidence and science for DiviTum 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 tests and its economic impact. The study with SWOG 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 and metastatic breast cancer each year that we aim to benefit from launch. With DiviTum TKa in clinical practice, usage can also start during the whole of the three 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 suggests monthly testing with DiviTum during the early period of a line of treatment, and then reducing to three monthly until disease progression. This creates, in total, an opportunity of 750,000 tests per year. To note, the number of test opportunities is slightly higher than we've shown in previous presentations.
The change covers the advice from oncologists such as Dr. Malorni, where they want to add this test at two weeks after the start of therapy to assess likely treatment response or resistance. Several other factors will influence the 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 a likely price for the test.
By the third full year of sales, we expect use in about 15% of eligible cases, with 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. I'd like to hand over to Henrik to talk about these new directions for the test.
Thank you very much, Robert. My name is Henrik Winther, and I'm overseeing the business development at Biovica. 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 Dako and Agilent Technologies, especially the companion diagnostic divisions. I joined Biovica approximately one and a half year ago, and I was very curious to know and learn more about the TKa biomarker because I think it has a fantastic potential within the monitoring of treatment. 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. Also provide you with an update on our collaborations in the pipeline.
That is both collaborations we have on the lab partnership side, both U.S. and E.U., and also on the pharma collaborations. 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. To really decide or make that decision, we made a thorough analysis at Biovica, and we used the four guiding parameters you see here to the left, TKa clinical utility, therapeutic fit, and market potential and competition, as those parameters that needed to be signed off for the individual indications.
If we start by number one, 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. Secondly, we also look for indications that have a therapeutic fit to our biomarker. 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. We look for those kind of indications, targeted therapies, anti-proliferative targeted therapies, I should say.
We actually also try to avoid indications that are typically treated with cytotoxic treatments, and that is because cytotoxic treatments are less innovative. Also they are more focusing on killing tumor cells, whereas we are actually focusing on treatments that are anti-proliferative. Very different strategy you could say. Also of course, market potential. We are a company and there needs to be a market potential within the indication we pursue. 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 metastatic breast cancer, we have avoidance of futile therapy and reduction in imaging. That actually has a great fantastic impact on the HE benefits. Same goes for looking for new indications. There needs to be a health economic benefit of using our biomarker within that new indication.
Competition-wise, that's also a parameter that we looked into. We don't want to enter into a field where the competition is really harsh. 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. That's the parameters we went through. 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 this indication passed our criteria. 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.
You need a biomarker that can actually at baseline, predict if the patient is going to respond to the therapy. 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 treatment is effective. Aggressive disease and therefore a need for this kind of a predictive biomarker and a monitoring biomarker is pronounced within malignant melanoma. A good fit there. Therapeutic-wise, actually within melanomas, there's really no use of cytotoxic treatment, chemo treatment because they're not chemo sensitive. 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.
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 these numbers for calculating the market potential. There seems to be a really good market potential. Health economic also are really important here and the malignant melanomas, there are big spending within therapy here because of the very expensive drugs you have. 85% almost of the cost cares that goes into malignant melanoma is due to treatment.
On a monthly basis, a patient would actually require payment of approximately $23,000-$36,000/ month and that is really depending on whether you are in U.S. or you are in Europe. It's less expensive in Europe. Again market potential and HE benefits are obvious within the malignant melanoma indication. Competition-wise we are actually also in a 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. That is one way of actually understanding if your treatment is working.
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. As you can hear, pretty complicated. Would be much easier just to use TKa as a monitoring device. All over here malignant melanoma we are in a really good spot and that's the first indication we want to pursue with our TKa biomarker. 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 Karolinska Institutet and Karolinska University Hospital. We actually achieved some very promising results.
It shows that TKa is a very strong baseline biomarker to predict response of these immune checkpoint inhibitors or IO treatments. 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 is also significantly better if you are TKa low. A very strong tool, TKa, in predicting response to IO treatment. Now we have the abstract out there in public from ASCO, and we also have a manuscript submitted to a peer-reviewed journal that is obviously done by Karolinska Institutet. 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.
The same way as we did for the metastatic malignant melanoma indication, we also dived into prostate cancer and into lung cancer. For prostate cancer, we have actually now locked ourself into that subgroup, which is called castration-resistant prostate cancer. That is a disease or a cancer that treatment-wise actually have a lot of biological similarities to metastatic breast cancer. For the non-small cell lung cancer indication, we have decided on the non-small cell lung cancer subgroup. Even further there, we have actually said our biomarker TKa is perfectly fitted for the advanced stage within non-small cell lung cancer. 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.
What I show here on this slide is, again, the market potential for all these three indications together. Metastatic malignant melanoma, castration-resistant prostate cancer, and non-small cell lung cancer, and divided into U.S., EU Big 5 plus Nordics, and Japan. 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 five-year survival rates and of course the mortality 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.
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. That is what goes into the overall target or total market potential, which is shown here. 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. 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 one is obviously the commercial setting where we want to support our product launch.
Secondly, we also want to establish collaborations with pharma where we can do TKa research use only testing. That is to support our scientific collaborators, but certainly also to support our pharma collaborations. 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. 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, that is where I want to go next. I want to give you a short update on where we are with our pharma services and pharma collaborations.
This is, of course, an area where we have the possibility of expanding our business, really to collaborate closely with pharma, developing diagnostic assays that are actually going to be released together with the pharma-targeted drugs 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 the cell cycle and thereby inhibit cell proliferation. Pharma focus is primarily on predicting response to their drug or monitoring response to their drug. 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 a monitoring test to monitor the effect of the treatment, it is still imaging that is ruling and less competition. That is why we have picked monitoring testing as the playing field of ours. Instead of calling it a companion diagnostic, we call it a monitoring diagnostic. We really have a two-track strategy within our monitoring diagnostic together with pharma. Track number one is really where we are building trust at pharma. It is both a trust in the TKa technology, but it is also our building a trust at pharma in our way of dealing with pharma, being professional and diligently actually make sure that we execute according to the plan we establish together with the pharma partner.
This track one is where we are currently, and that is also the track that is, over the last six, seven months, has really picked up momentum. We now have four or five project activities together with pharma in this track. It's more preclinical and phase I activities with pharma. It's strongly picking up, as I said. This track is actually what allows us to move into what we call track two, which is really developing companion diagnostics or monitoring diagnostics together with pharma. This track number two 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 collaborating. This track is, of course, about really developing, registering, and commercializing these companion diagnostics together with pharma.
The beauty about this track two 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. It's about pharma really paying for having this companion diagnostic test developed. Why would they do that? 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 safer use of their drug, they can differentiate themselves from competitors. What is shown here on the left is, on the yellow bar, is really that we undertake the development for pharma through a fee-for-service agreement.
We are paid on an hourly basis to develop the companion diagnostic. Afterwards, the companion diagnostic, together with the drug or alongside the drug, is released to the market, and Biovica will get to own that product and also to own the revenue coming from that product. This is track A and B shown here on the left. That is, of course, very attractive because you get a chance 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.
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. That will typically also lead to that our core business products will find their way into these labs. That's the positive feedback loop into the core business, you could say, based on the companion diagnostic products. On the right side of the slide, more details on the revenue potentials from each of the tracks I mentioned earlier on strategy-wise. Track one, as I said, it's the early collaborations with pharma. It is activities, mainly focusing on phase I and pre-clinical. It's less fee-for-service revenue.
I think you have seen lately, perhaps if you looked into our financials, that we have sold quite a few kits, that is exactly coming from these collaborations. It's certainly not insignificant revenue that we receive through these track one collaborations. The real upside is, of course, track two, when you move into a true development registration and commercialization of a companion diagnostic. There are some numbers shown here on the potentials of releasing that kind of products. I should say from a fee-for-service perspective, these projects could be between 17,000, 20,000 hours, also paid to a certain hourly rate. Also a decent fee-for-service revenue coming in there. That leads to a yearly revenue potential per CDx as also provided on the slide here.
Yeah, I think overall, we're looking into a bright future with our business development activities and coming activities, new indications. 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 monitoring of metastatic breast cancer in the U.S. and the launch of the product for that use, we have actually initiated a lot of activities to widen use over time. The white marked arrows are the ones where we're making investments, and we're making an investment now and have been down for quite some time to launch the product. Really soon now, we expect in the quarter three, the regulatory approval or clearance in the U.S. That will be the starting point to build revenues to three years after launch, reach 50% of the market potential. We expect over time peak sales of about 50% of the market potential.
As we also told you, we are looking already now into the European countries, focusing on the top five in the Nordic countries. Before end of year, we are expecting to be able to launch in the first European countries, and then widen use within that region as well. The third focus area is the Japanese market, where we together with a partner, will have to expand our regulatory clearance, so that will be an additional activity for Japan. In that, we can also build on the strong data set that we have and the collaborations within the breast cancer area. 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.
That will require new regulatory processes supplementary to the current 510(k) intended use. Also there we can benefit from the fact that we're included in these type of trials 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. Also having launched the product on these three markets from metastatic breast cancer, we have established sales channels, collaborating partners, and commercial agreements with labs and so on. That launch process will be a lot smoother and simpler than the initial launch within breast cancer. As Henrik talked about, we are looking into new indications outside of the breast cancer area. First of all, metastatic melanoma.
We have a proof of concept that is being currently presented on ASCO, and 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. We're looking also to these three 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 is $400 million-$700 million/ year for these markets, and the locally advanced will add another 30%-40% to that market potential. If you look at the additional indication, that is also adding a big market potential within these three areas. The last one, companion diagnostic, where we can leverage the fact that we already have pharma as customers using our assay for developing new therapies 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 one of the collaboration. Of course, the real potential is determined on the potential of the new therapy, but when the therapy reaches the market, also us as a diagnostic company providing companion diagnostic will benefit from that as well, and will drive sales of the diagnostic product. Yeah, a lot going on, although the focus is still on the U.S. launch. We have initiated and have activities ongoing in several areas currently. 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.
The collaborations with leading opinion leader and academic centers has resulted in a strong set of clinical data proving the value for the product. That is the foundation, the basis for all our commercialization activities. 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 three this year, which will be the starting point for our U.S. launch. Before end of 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. There's a lot of milestones to look out for the remaining part of 2021. Thank you very much for listening so far. It's not over yet because we will open up for a Q&A session.
For that, Charlotte, please, and Henrik.
Thank you, Anders. Henrik, please. Thanks. Amazing to see you have so much going on, Anders, in your fantastic company.
Yeah.
Yeah.
Well, it's a great team.
It's a great team.
There'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. Of course, we all do it because I think a strong motivating factor for all of us is 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 pose them at ir@biovica.com, and we'll try to manage them as we go along. Coming back to all that's going on here and the milestones that you put up, starting with FDA clearance.
Yeah.
You said already in January that you expect Q3.
Yeah.
Are you more or less certain now that you will reach clearance in Q3? 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. Initially, we were in discussion, then there was a 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'll be able to come back with the results. Yeah, with that in mind, I would say that I'm more confident now than when the process was kind of halted. Yeah.
More confident now. Now we actually have yet another question from Redeye on this FDA approval. When do you expect to be in a position when advanced breast cancer is covered by the FDA approval, one year after the initial approval? Do you dare say anything about that?
Locally advanced?
Yeah.
Yeah. We have to come back with detailed timelines on that. We haven't disclosed a milestone for that, but we are already included in clinical trials within locally advanced as well.
Okay. Previously you've said that you'll sign a partner in connection with FDA clearance. Henrik is saying you're already in discussions when it comes to the clinical use, so to speak. Sorry. Yeah. Could you just elaborate on this? When do you expect to be out in the labs?
What we're doing is we're obviously discussing with several laboratories primarily in U.S. initially, but also preparing for Europe. Discussions are research use only. These are the agreements we have in signing now. Also expanding the discussions with these partners on actually having them carry our assay as an IVD test, a commercial IVD testing. That's where we are currently with our discussions with lab partners.
I think that the market has thought that these being as an IVD test, that would be when you get the FDA clearance.
Yeah.
How fast can that happen, before or after FDA clearance?
has an efficient process as possible. 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 that way we have an efficient process, and we can gain time to market.
We have a question from ABG as well. Have you started to establish any best practice or protocol for how often patients should be monitored?
Yeah. I think, Robert, you covered that briefly. Want to elaborate a little bit about that?
Thanks, Anders. What we've done on this is we've con sulted with oncologists, both looking at their clinical trials and looking at how their practice actually is. 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 two weeks after the start of treatment. Their expectation is at baseline, two weeks after the start of treatment, monthly thereafter during the early part of treatment, up until six 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 three months. 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.
There is a follow-up question on this. Could you go into more detail in what sort of things you're looking for in a partnership? Is that for you, Henrik, perhaps?
This is for that one. Henrik?
Yeah. We're discussing several things. Of course, kind of the terms under which we are to operate with that partner. Primarily, it is to be a lab that has a certain coverage, because we need to have a certain coverage for our test. It's not going to be only one lab, it's going to be several labs, obviously. I think, coverage and then terms on pricing, I guess.
I'll continue with the ABG questions. How does the DiviTum predictive difference in progression-free survival compare with other biomarkers?
Predictive?
The predictive difference in progression-free survival. 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-free survival or overall survival because they typically don't undertake that kind of studies for a biomarker. We had a chance to chip into this SWOG trial and come up with PFS and OS. I guess also some of the studies presented by Luca, because we are tightly connected to therapeutics and the monitoring of therapeutics. I guess that's why we have the PFS and OS data strongly. Otherwise, typical biomarkers within the diagnostic world is more sensitivity and specificity. It's a different story, I would say.
Okay. Yeah, we have some questions also from Pareto. Could you elaborate on your product launch readiness?
All right. By product launch readiness means?
Have you already started some additional marketing efforts outside KOL networks? How are you building up the sales force in the U.S.?
Yeah. Okay. That's one aspect. Another aspect is securing the production process and the supply. I can start with that, or you can start, Robert, with the sales pieces, and I could complement with the supply. Is that okay?
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. Second, 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. We're moving forward step by step in several different areas. Anders?
Yeah. That's good. 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. Yeah, we're preparing to get great awareness for the product. Maybe the supply side of things, if we create demand, we need to be able to meet the supply. In parallel with developing everything for the 510(k) 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.
That goes hand in hand with the product development. We also have done a production process development. Yeah. We have invested time and effort in that as well. That's based in our facilities in Uppsala.
You are more sure than before on FDA clearance at the end of Q3.
Yeah.
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 a year's time in the U.S.?
In the U.S., Robert, maybe you can start, and maybe I can complement with Europe.
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 a 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. I also think, as Henrik indicated, we should have the necessary lab arrangements in place comfortably within the next 12 months as well.
Europe, we're also progressing, although it hasn't progressed as far yet as in the U.S. 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. 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?
Yeah.
To do all this?
We are well-funded, is a really short answer. 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 million. Also, we expanded our shareholder, getting some more institutional investors in to complement the already strong shareholder list. We at the time also had cash at hand. 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.
We have some outstanding questions on your studies. There is one from Redeye. How many prospective studies have been completed? How many are ongoing, and when can we expect these to finalize?
That's for Henrik.
I think we have one completed prospective study.
Yeah.
We have two ongoing, and we have a couple in pipeline.
Just like.
Yes.
Amy talked a little bit about.
Yes.
Amy had a slide on this, actually, and Luca presented also, so I think you're right. The completed one is the PYTHIA trial that Luca had slides on, and it's completed, it's been presented. What he said, it's about to be submitted any time soon in his presentation. You can expect a couple of months, up to six months, before publication. That's the process normally.
We have a question, I guess you are already approved in Europe, but the question is, when will DiviTum be submitted for the European Medicines Agency? When is it expected to have it approved by EMA, and are there any additional approvals necessary for commercialization?
Yeah. That's a good question because we already have CE marking. We have further developed a product, as I said briefly in my presentation, and it's the improved version that we're going to the FDA. 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. We'll do it with the current standard before launch in Europe by end of year. Then we are also well-prepared for the coming standard, which will be applicable mid-next year, you can say. 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've 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. That's why it's important to do it that way, 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@biovica.com.
Send letters, yeah.
Ask any more, I'll get them in the computer and ask them for you. I had a question. You are on the ELISA platform, and it's not the most modern. Do you have any comments on that?
Yeah, we can come out and have it. Do you want to comment on that? I know that this is an area you know well.
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. If you really want to enter the market with a new biomarker, 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 posed all of them. I'll leave the floor for you, Anders, if you have any concluding remarks, but you've said it all.
I've seen the number of participants. I'm grateful for the interest, and I thank you all for participating, I thank to my colleagues and to Dr. Malorni, and I'm sure that with our very exciting product, DiviTum, that can create a lot of value both for cancer patients and healthcare providers. I'm sure also that will translate into shareholder value for our shareholders. Thank you very much, and we're looking back to update you on our coming progress. Thank you.