First of all, thank you, and welcome to be here. This is a very important day. I know that every meeting starts with a very important day, but believe me, it is true that this is very important for the company. Let me spend some minutes just to remember when we started, and where we are now, and where we are going. Maybe Alessandro and the other team tell you later. We started exactly 22 years ago, and we listed the company in 2007. Since the beginning, my personal interest was not to develop a me-too company, but to develop something that must be new in terms of concept, in terms of approach, in terms of everything.
When developing our first technology, that is MMX, I remember that a lot of people that at the time were advising me, they tried to push me and the company, the drug delivery segment, but I was not really convinced because for me it was more important to try to develop a specialty pharma. Using the technology, we decided to enter in the colon area just because I realized that the technology has property to be a real new concept. Thanks to this decision, we became, and we still are, the leader in the IBD sector. Our two brands, Lialda and Uceris, they sold more than EUR 2 billion. Thanks, let me say, this decision, we are the only and unique company that has been approved three products that belong to the same technology, MMX, because we approved Lialda, we approved Uceris, and now was approved Aemcolo.
Starting from this point, what I do believe, and what I still believe that is important for the company, let me say, having always a target. Our target in the last 10 years was the colon, and in the colon, we developed a series of products, and one of them is methylene blue. I know that when I talk about methylene blue, it is something that is like a pain because the company is like Jesus Christ, before Jesus Christ and after Jesus Christ. Methylene blue for us was before methylene blue, after methylene blue. Now we are still alive, and it is something that is in the DNA of the company. We never give up. It's something that I learned from my father. This is important. From a problem, because methylene blue, one year and a half ago, was a problem, we try to approach differently.
It was from a problem in a very great opportunity that can be a game changer because you have to know that thanks to the library that we got through the clinical phases, especially the phase III study, now we can play in the endoscopy world that is more than 35 million procedures, something that can be a game changer. Let me say, something that you are present is something that can be like the "Star Wars." Something that changed the world. For the colonoscopy, it's like methylene blue for us, is before the artificial intelligence and after. I don't know if we will retain a large part of this market, but I know that first, we will be the first company to launch the product in the market next week in Europe, and in January in the U.S.
Second, we have just closed last, the biggest medical device and hospital organization that is Medtronic. Thank you, and I leave to Alessandro.
T hank you very much, and welcome. Thanks for coming. As Mauro said, it's a very important day for us. Just to outline the program, and you will see some new people that will be speakers today. I will introduce on company perspectives and strategy, and I will give you some insight of the latest deals that we have done. We will have two new very significant addition to our team, Yann Gaudin and Andrea Cherubini, that will speak about the artificial intelligence. They are, respectively, the head of research and development of Cosmo Artificial Intelligence. That's a dedicated company that we have created for the project, and the head of artificial intelligence, also of Cosmo AI.
We will tell you what we plan to do with Aemcolo. This will be introduced by Sean MacDonald, another new addition. Sean MacDonald is our new Head of Business Development.
We will speak about the new products in the pipeline. There will be an introduction by Professor Michele Maio, and then the product will be described by Mara Girolami. Mara Girolami here is indicated as the Chief Scientific Officer of Bellatrix. Bellatrix is the name of the company that we have in San Diego that runs our biotech lab, and therefore, she will introduce you on the concept of the new product. Finally, we will have a wrap-up and Q&A questions. We'll be more than happy to answer to any question you may have. This may look excessive to someone, but this is the message that we want to convey. As Mauro said, never give up, always strive to move forward at full throttle. As I was saying to a colleague of yours just a few minutes ago, things may go right or things may go wrong.
I think that the important thing is that you have to feel confident with yourself that you've done all that you could. I think that this is the important thing. This is what makes you feel okay, that you have tried to exploit every opportunity that you had, that you've leveraged on the inconveniences to try to build new opportunities. Let me tell you what happened in the very short period that was actually between our presentation of the financial data at the end of March and now at the beginning of May. As you can see, it has been a month and a half that was very rich of event. They were all carefully planned in advance. They all happened on a roll, but they didn't happen by chance. They happened because there was a tremendous amount of hard work behind it to make it possible.
First of all, we have unveiled our artificial intelligence product and the subsequent worldwide validation deal with Medtronic. It's important, this concept, the validation deal. I think that if we would have told to the market that we had developed an artificial intelligence product, the market would have probably thought that we were completely crazy. Certainly, we didn't develop this in a month or two. This is the fruit of a work that lasted years. We've been very careful, and while we were continuing the development of the product, we kept the news for ourselves until we were able to communicate to the market something that had to sound like validation. Medtronic is the largest medtech company in the world, is the leader in medical technology.
You can only imagine the amount of due diligence that a company like Medtronic would do before stepping into a deal like this. This is an exclusive distribution agreement worldwide. This means that Medtronic will sell this device around the whole world. This is going to give us an unrivaled capacity in penetrating all markets from the U.S. to China. We have simultaneously signed a distribution deal of Eleview with Medtronic for the U.S. and adding China and adding South America. The other jurisdiction actually have been licensed to FUJIFILM, and Japan has been licensed to EA Pharma. Again, this gives you a very, I think, thorough insight on what the potential of Eleview is if, again, a player of the caliber of Medtronic really wanted to enter into an exclusive distribution agreement for us.
We have also signed another thing that may be played down in our press release because people may not understand. Not only we've signed those two deals, we also signed another deal with Medtronic, which is probably even more important than the other two. This is a collaboration agreement in artificial intelligence. Medtronic will rely on the collaboration with Cosmo to exploit new opportunities and study new products. I think that this is really something that tells you that we have an expertise in-house that the market should hopefully start to properly appreciate. We have submitted with only nine days of delay in respect of our timeline. We've submitted the NDA of remimazolam. The brand name BYFAVO is now being approved by the FDA. From now on, remimazolam in our presentations will be called BYFAVO.
We have seen the FDA accepting the IND of our new oncologic product on which Mara Girolami and Professor Maio will tell you about later. We have completed the restructuring of Aries. We expect to have approximately EUR 20 million savings in 2019. Although this pertains to a company where we only have 45% off, we're very proud to see that Cassiopea had very positive results for the phase II clinical trial of Breezula. What's Cosmo? Well, as Mauro always points out, Cosmo is difficult to understand. Cosmo doesn't really stick to conventional models, and I understand the difficulties that analysts or investors may have in figuring out exactly what we have and how to take into account the opportunities. Really, we are a sum of very different businesses and assets.
We're a very complex organization, and our aim is just to efficiently develop and manage our products while trying to reduce as much as possible the overall risk. This is the company that has created Lialda, Uceris, Eleview, Aemcolo, now the Cosmo AI, BYFAVO, Methylene Blue MMX, CB-03-01, that has got a 45% stake in Cassiopea, that still retains the contract manufacturing activity. You can see it's a complex organization that's not run by many people because we don't like overheads. We try to keep overheads under control as much as possible. All of these different items are actually different businesses. It's very difficult for us to be described in a very simplistic way or with a simplistic model. There's no such a thing in order to capture what we really are in a nutshell. We are a sum of different businesses and there's a lot.
Sometimes when I discuss with Mauro, we try to make sense of what's happening into the market, we think of the following. Currently, as of today, we have available cash of around 400 million CHF. We have a stake in Cassiopea, whose market value as of today is around 235 million EUR. If you assume that Cassiopea is a sellable asset that can be counted together with the cash, that's over 635 million EUR cash. We consider the cash that we have, basically net cash. We have issued a convertible bond. I will tell you a little bit more about that in a minute. We have issued a convertible bond that can be reimbursed with shares.
We continue to be not completely sure that the market has fully digested this. If you consider the number of shares that we can issue at our will to reimburse the bond, you should consider our current market cap as expressing a fully diluted situation. Therefore, we consider our cash as net cash because the convertible can be reimbursed in shares. The math is simple. As I said, it's around 635 million EUR of liquid or sellable assets. The rest to match our current market cap is composed by all these opportunities. We would like everyone really to think at each one opportunity as a standalone opportunity that should be worth a standalone valuation, just in order to understand what happens if you put all these things together, and what is really behind our share.
This slide is entitled Cosmo Strategy Going Forward, maximize returns while minimizing risk. As our friends of Cosmo AI will tell you in a second, you can easily imagine that the Cosmo AI product is not the fruit of a one-night stand, but has been developed through years of hard work. By the way, we said unveiling of the product, every one of us can see the product. It's that white box on the table. The product exists, it's there. It's in front of Yann and Andrea Cherubini. It looks like no fancy. There's a lot of hard work and a lot of intelligence inside that white box.
More than us.
More than us. Well, no, not more than us, because we don't think that robot will ever be as intelligent as the humans, hopefully. We'll see. But it's important that you understand the following. This has been going for a while, and we knew that it wouldn't have made sense for us to announce the existence of this product if we weren't able to validate this in some form. In the meantime, our original plan was to go alone in the U.S., and this is the reason why, without saying anything, we issued the bond. The idea that was behind the bond was to finance the build-up, the set up of an even more structured sales force and marketing organization to be able to market the artificial intelligence ourselves. In the meantime, we were.
Transform the bond in James Bond.
James Bond.
James Bond ready.
We said we will not know whether we will be able to strike a very good deal with anyone and what the feature of this deal would be. Let's just get ready to go full throttle, as we said at the beginning, to go full throttle alone, making sure that we have all the resources that are needed to exploit this opportunity by ourselves.
In the meantime, we were having discussion with several players, with several big players in the med tech area, we realized that it would have been much better for Cosmo and much better for the shareholders and the stakeholders of Cosmo to see if it was possible to do a very good deal with the largest player in med tech that would grant us not only just an unrivaled market firepower in the U.S., but also in the rest of the world simultaneously. Because we might have been able to build up an organization in the U.S., but certainly not an organization that would have been able to market this worldwide.
This was the reason and is the reason of the deal with Medtronic, this is also the reason why once we've been able to strike the deal with Medtronic, basically the equity that we had raised with the convertible was not actually necessary anymore. We'll tell you about that later when we will discuss the outlook. It's important that in a prudent fashion, we wanted to make sure that we had already everything that was needed if we wouldn't have been able to go and close a very good deal. Instead, I think that we closed an excellent deal with Medtronic. The territory is worldwide. The distribution agreement includes the supply, therefore, we will be the manufacturer of the device. We have an estimated net margin for Cosmo, which is above 20% of sales. This is not really a distribution agreement. This is a real partnership with Medtronic.
We're not disclosing what's the overall participation that we have in the revenues that will be generated. What we can tell you is that our estimated net margin for Cosmo is above 20%. In a certain way, the revenues that we will have are very close to profits. The devices are already currently being deployed with European key opinion leaders. They're preparing the commercial launch. As Mauro said, this will be launched officially, Mauro, in about a week, right?
Next week. Yes. The kickoff meeting was yesterday.
The kickoff meeting was yesterday. European Union sales are expected to start in the second half of 2019 or even before, according to the kickoff. The U.S. sales are expected to begin in 2020 upon the FDA approval. We have regulatory pathway discussion ongoing with the FDA. Maybe this is something that can be discussed later on, either separately or in the Q&A session. We expect to begin sales in the U.S. by the beginning of 2020. Medtronic has decided to use a very established business model that they've already used in different contexts, which has been very successful. This is going to be user fees. The hospital and the institution and the endoscopy cabinets will not have to buy the product. Therefore, they will not have to enter into a more lengthy and costly capital sales equipment management.
Those will be made available for free, and every user will pay a fee for every device. Medtronic has already estimated that the minimum yearly fee for a device, both in U.S. and EU, will be around EUR 3,000 per month/euro, which means an estimated yearly fee per device of EUR 36,000 at onset. The estimated number of colonoscopes in the U.S. are at least 20,000. One can easily do his own math and figure out what the initial dimension of the potential market just in the U.S. It's a big market. It's a very huge market, and we will let do your own speculation, the assessment on what kind of market share of this potential market an organization such as Medtronic will be able to exploit and capture. We believe that they are the best players in the world, and their story confirms this.
We're proud to have been able to partner such a device worldwide with them. Along the same line, because we were getting very close to a deal with Medtronic, we decided that if we could do a deal with them, frankly, it made no sense for us to continue the direct distribution of the medical devices in U.S. through our own organization. Therefore, we decided to stop the direct distribution of the medical devices in the U.S., having signed with Medtronic a new distribution agreement as a partner of choice. This new distribution agreement, which includes supply, has been benefit of immediately extending Eleview to China and South America. Most of you, I guess, probably know that nowadays, the Chinese market is considered the second pharmaceutical market in the world after the U.S., because it has overtaken over Europe.
This is certainly the most promising market, therefore, the fact that both, if you think of it, that both AI and Eleview will be distributed also in China by the biggest player in the world, it's something that allows us to a certain degree of comfort. Because of this, because of what we had in mind, we've decided to change the nature of our U.S. commercial organization and just to position this as an organization that will be used on an opportunity by opportunity basis. When this was born, when Aries was born, the idea is that we would have conveyed through Aries all of our products that could be sold in the U.S.
We have decided for the reason that I hope you share with us, that it was tremendously more effective for us to have the biggest player in the world enter into worldwide distribution rather than trying to sell the stuff ourselves. This is something that will entitle us to a very significant share of the profits without running the risk and without bearing the cost of a huge commercial organization. Aries will be used on an opportunity by opportunity basis, depending on what we decide to do. Cosmo, I think, is proven to be a very flexible organization. We frequently change our mind.
Every day.
Every day.
Every day.
Well, sometimes even more than once in a single day, but this doesn't matter. This is the fruit, I think, of good discussion and trying to capture the opportunity. Again, as Mauro stresses, we don't have a model. We are opportunity driven, and because we thought that the opportunity in the medical device and with the AI was much larger partnering up with Medtronic, we were very happy to say, "You know what? Even if we build Aries for the purpose, even if we have raised the convertible for the purpose, we think it makes more sense, and we will end up making more money by partnering up with Medtronic," which is exactly what we did. It's not only because we have decided to set up Aries once, that then everything has to go necessarily through Aries.
It will just depend on the circumstances. We will try to do what we believe is more convenient. What are we going to do? Sorry, just one second. Back here. We decided that we were going with Medtronic with the AI, and because Medtronic was also very, very keen to be the distributor of Eleview and expand the franchise in China and in South America, you understand that there was no reason for us to continue bearing the cost of the commercial organization in Aries, which is the reason why we decided, and this is one of the good thing of the U.S. market, that you can intervene and cut costs very quickly. We decided, "You know what?
We're going to lay off our sales force. We can save EUR 20 million in a year. Then we will decide afterwards what is going to be more convenient." We have kept the managerial infrastructure. Therefore, if we change idea again, it's not going to be an issue to go back on our steps. We thought it was more important to save a lot of millions immediately for the benefit of everyone. What we have done in the meantime, we have identified a new direct marketing strategy for Aemcolo that will allow us to maximize the sales without a field sales force. I don't want to anticipate what our colleague, Sean, will tell you. Mauro also has a lot to say about this, but I think that we will be doing something interesting that has a very high potential of success.
At least this is how we see it. I don't want to anticipate too much. BYFAVO, just for the sake of it, I remember this is remimazolam, and you may not like the name as I don't like the name, but I can tell you that the other available names were even worse than this. I can just let you imagine what they were sounding like. With BYFAVO, we're now pursuing the NDA approval. We will see around April what the FDA thinks of this. Actually, the NDA has been submitted, and we're waiting for the first response to see whether the NDA can proceed. This should come at actually 60 days after the NDA has been submitted. Therefore, we should know something from the FDA by the beginning of June.
With Methylene Blue MMX, I think I told you the story extensively at our last financial highlights presentation day. We are now crafting the new protocol for the additional phase III. We will quickly engage with the FDA now with the aim of being able to start this new trial by the beginning of next year. CB-03-10, it's the code name of our new oncology product. Again, Mauro together with Mara will tell you more about what we intend to do. It's just important that you don't think immediately that we're going to step into a very extensive and expensive clinical development of an oncology drug. I think that one of the things that characterizes Cosmo is that Cosmo doesn't try to do what it doesn't know what to do. The idea is that we would like to bring this through a phase I.
We have already received a manifestation of interest from very big players. Of course, we believe that the value of the asset could significantly increase if we complete the phase I and give indication on early activity signals. This is what we will try to do. The idea is to partner the subsequent development with a high-standing player. I will now pass the word to Yann Gaudin and Andrea Cherubini, that will walk you through our new device. Of course, there will be all the time afterwards for questions and answers. Thank you.
Ladies and gentlemen, good afternoon. I am very excited to be here to present this project. It has been a long time. We are working on it four years, I think, three to four years. This is a groundbreaking project about artificial intelligence. First of all, I would like to introduce the team that has been working on this project since its first infancy. Myself, Yann Gaudin, the head of research and development, Andrea Cherubini, head of artificial intelligence and machine learning. Another key person is Giulio Evangelisti, who is not present today. He is the Head of Production and Delivery. This team has been working for more than 10 years on hardware and software products. Delivering them to the pharmaceutical market, as well as healthcare in general, in the space of neurology, radiology, cardiology, dermatology, and finally, gastroenterology.
I would like to provide you a brief overview of the project history. Back in 2013, Cosmo was at the beginning of the Methylene Blue MMX clinical trial. At that time, due to regulatory requirements, Cosmo made a key decision, was to record all the videos using the highest possible quality. That was a decision that was crucial. At the time, there were no recording units that was available to record videos in such a way. As a team, we worked on the development of such a technology, and we succeeded in developing the technology. We deployed that technology to investigational sites, and between 2013 and 2016, we've been recording all those videos that were belonging to the clinical trial. More than 1,250 full colonoscopy HD videos, together with all the relevant clinical information, histological information.
Building this huge database, that then started to be the foundation of our AI project, which started in 2015. At the very beginning, we started with some experiments, and then we had a dramatic change also in the success of our technology between 2017 and 2018, when we got outstanding results. That paved the way for the finalization of the product and the development of the medical device. Before getting into the description of the device, I think it is wise to describe the context. We are speaking about colonoscopy, and we are in the space of colorectal cancer. Colorectal cancer is one of the leading causes of death today. It's the second or the third leading cause of cancer-related deaths in men and women, respectively. Detecting and removing polyps is crucial to impact mortality.
If we have a 1% increase in the adenoma detection rates, which is a rate for precancerous lesions, then we have a 3% decrease in the risk of interval cancer. As you may understand, colonoscopy is not a perfect procedure. There are situations in which endoscopists are going to miss polyps. This happens very often, and unfortunately, the reported miss rates are between 20% and 40%. It is a huge number. One of the ways to reduce this number of missed polyps, is to have a second experienced observer assisting the main endoscopist during the procedure. We concluded, and we had the idea that a real-time automatic polyp detection system can assist the endoscopist to perform a more precise procedure, and it can assist also very reliably as it is a machine, and as opposed to a human being.
We thought also that the machine could act as a second set of eyes, but a set of non-blinking eyes. Starting from this idea, we also understood that a device like that one is what is called a CAD, a computer-assisted diagnosis tool. A CAD can be built with AI or without AI. We decided to build a CAD with AI. We decided also to build a CAD with a particular type of AI, deep learning. Essentially, deep learning mimics the way human brain works. I'm very proud to present the product you've been seeing also on the table. I'm showing this picture that shows the device on the lower shelf of a standard endoscopy cart. This is a very common cart you may find in every endoscopy room, and it's carrying also some standard endoscopy equipment.
An endoscopy display on the top, on the middle, a video processor, a light source, and the endoscopy probe. We added our product on the bottom. So this is the front view. I don't know if you can see it on the table, but this is just for convenience. The back view. Of course, what is CB-17-08, which is the code name of the product, able to do? It is able to receive a stream of video coming out from the endoscopy unit and superimpose digitally, overlay in real time, markers to highlight interesting feature. This stream can be then displayed on the main endoscopy display, the already existing endoscopy display of the unit. What is important to say that those markers are markers that are indicating potential lesions. Everything is done in real time.
A question would be then how it works. I was saying before that we use a deep learning. Deep learning is a specific class of algorithms that is a specific class of artificial intelligence algorithms that are able to learn. You can teach them to do something. You can teach an artificial intelligence algorithm, a deep learning algorithm, to detect a lesion, for instance. You have to submit, you have to train the system using very good data and a lot of data. It is very important to have those two requirements, otherwise, you are not going anywhere. Well, we have the best data set in the world to do that, which is the data set that has been collected during the Methylene Blue MMX clinical trial, the phase III trial. Why it is the best data set in the world?
Because it has a very high quality, because we have lossless quality. I mean, we didn't lose anything. We have a very large amount of videos. We have the two requirements. By the way, another key factor is that endoscopists that performed the procedures that were recorded were averaging an ADR of 47% in white light, which is a very high ADR, which is a key performance indicator for endoscopists. What are the advantages of having these data sets? First of all, we collected many videos coming from many sites. We have also collected many videos coming from many endoscopy units. We were able to train the system and be able also to train the system with data coming from a broad range of manufacturers. We are very consistent and very robust across manufacturers.
We can plug our system to every endoscopy units in the market today. A second advantage is that, we recorded a large data set coming from an international population. Again, the algorithm is very robust across all the people that are going to use it, I mean the patients, for every country and every region. Again, coming back to the high ADR of colonoscopists that performed the procedures that were recorded. Having the privilege of having those recordings means also that we were able to have also very difficult-to-detect lesions be listed and annotated. We were able to train our AI to recognize those hard-to-find lesions. We could transfer this knowledge to the AI. By the way, I was mentioning also the quantity, which is crucial.
We leverage all the potential of the data set, and we extracted from the data set over 700,000 images to train the AI, which is a tremendous amount of data. Of course, we are not stopping here. We are continuing to receive videos, and we are improving more and more, by the end of the year, we will be reaching numbers in the order of tens of millions frames. You can imagine how we can improve. I think the best way to get a feeling of how the technology works is to take a look to videos. Well, it's just flickering a little bit for technical problems. This is how it looks like a colonoscopy procedure. I don't know if you are familiar with, but it looks like that. The procedure is a very short procedure.
It is a 6 to 10 minutes procedure. The probe is moving very fast, and everything is running very quickly. In that space, the endoscopist also has to do a lot of things. He has to manage the patient, depending on the sedation type. He has to manage the team to collect all the samples. He has to manage everything. In the same time, he has to manage the probe, to orient the probe correctly, also in very difficult situations sometimes. We are bringing to the market a revolutionary technology that allows the endoscopist to have a help, to have a green square around a potential lesion. When everything is moving, the physician can be notified in time about the presence of a lesion. We also can see that on the second video clip I've brought.
This second video clip is another example that shows also how consistent is the device in alerting the endoscopist about lesions. Here we have 2 flat lesions, very hard to find on a site, and they are framed very consistently across the field of view in any position, even in the dark, even far away. It's very consistent, it's showing that it's able to provide some annotation, some squares, even for multiple lesions at the same time. It can reach a tremendous amount of lesions at the same time. I think up to 32, which is a number that is very high. It never happened. Taking a look to the third clip. This is another interesting situation, a little bit more complex. We have a main lesion you can see on the center left of the screen.
maybe the endoscopy is directing the attention to that spot and is well-framed. There's an additional lesion on the right. There is an additional lesion that is appearing, and this is a typical situation. Endoscopist, maybe they are concentrating on a lesion, and they are not seeing other lesions that are in the same space. This is going to alert the endoscopist there's another lesion. He can process both according to standard of care. I have a collection of other clips that are very short clips that are showing almost the same as the clips before. Essentially, they are showing how quickly a lesion can appear and disappear, and how quickly the system can instead be proactive and alert the endoscopist.
In a typical endoscopy procedure, even if a lesion is appearing very shortly, the system is able to alert the physician, the physician can take action, direct the probe to the lesion, and then assess the lesion independently and perform resection if necessary. This is, I think, very representative also of the variability you may find in colons about the mucosa, about the bowel prep, about the lesion type, about movements, about artifacts, glares. You can see how consistently and reliably the device is delivering the expected performances. I think we can get back to the presentation. I would like to provide some numbers to explain the performances. Not only seeing some clips, but seeing also some numbers. Well, the huge video library we had was divided in two parts. One dedicated to training.
The vast majority of videos were dedicated to training, to train the AI. A small part was dedicated for validation, and it was never submitted to the AI. We had the possibility to test the AI to understand what are their performances. Basically, we submitted this validation set once we trained the AI after training, and we recorded results. We compared those results with the findings of the endoscopists that performed those procedure that were submitted. This comparison allows us to calculate sensitivity, the true positive rate per polyp. That shows a score of 99.7%, which is a very high score. That is meaning that essentially, the device is detecting all the polyps. Another important indicator is the activation noise. We have to analyze false positives, false activations, I would say.
To understand how false activations are present and to also understand how many of them are present, We've submitted the validation set to the AI. We picked up all the activation in every frame of the video. The video is a collection of frame, 25 to 30 frames in a second. All the activation were retained and then submitted to a panel of endoscopists. Those endoscopists told us if the activation was a true activation, was good, or if it was a false positive. At the end, we divided the number of false positive over the number of frames, and we got this parameter, which is the activation noise. We have an activation noise of 0.9%, which is very low, and it's telling us two things.
One is that the system is not going to disturb the endoscopist during the procedure, and the other aspect is that the system is framing only polyps, essentially. We have these two important items. One is sensitivity, it's telling that the system is detecting all the polyps, and the second one that is telling us the system is detecting only polyps, which is very important. If you remind, I was speaking about the second set of eyes. We definitely brought to the market a second set of eyes, always present, always active, that everyone can use.
Not expensive.
Not expensive, I would say. Everyone can use, every endoscopist can use. It is ready to use, it's there. It's a second experienced observer? Yes. It learns from the best endoscopists. I showed how we can say that. This is our second set of eyes. A few words about our R&D. Of course, as you know, in a project like this, you have not to stop, and we are not stopping, definitely. I was anticipating before, we have a very huge work in extracting more information from videos, collecting more videos to empower the AI. This is going to continue in the following months. Of course, we will be releasing updates regularly to the customer base. We are working on new core functionalities.
Those are already under development, and I'm referring especially to virtual biopsy, which is a feature that allows to automatically detect the nature of the lesion. I've shown the product today is able to detect lesions, and we are working on additional functionality that try to guess the nature of the lesion, which is a very interesting feature. An additional set of application in the GI space are under development as well, especially in the field of IBD, which is very important, and then also gastro as well. Because this platform can deliver the same kind of results also in other spaces. Of course, additional features beneficial to patients and physicians as well will be implemented in the forthcoming months. What's next? As Alessandro was saying before, the device is already approved in Europe.
That means that we are rolling out to key opinion leaders in Europe. The device will be presented at DDW next week to the public. The FDA regulatory part is underway, and we expect to enter the U.S. market by Q1 2020. Thank you.
Thank you. Now it is the turn of Sean to walk us through. Please, go ahead.
Catching the attention after this presentation make very difficult because you can imagine that, as I said at the beginning, this can be a real game changer in the colonoscopy procedures. So is in our DNA. What we are going to present is not a revolutionary product, but revolutionary is the way that we're going to present, and I leave to Sean that is much better than me, okay, for the presentation.
Great. Before we head upstairs and start shaking everybody's hands, and before we start eating food prepared by strangers, I'm here to talk to you about E. coli transmission and diarrhea. At least a little bit, because the product that I am speaking about is Aemcolo, and this was a product that was approved by the FDA in November of last year for travelers' diarrhea. I believe the majority of you are already familiar with it, familiar with the approval. What I'm going to walk you through today is the go-to-market strategy that we've developed in order to fit within the theme of the presentations today of trying to maximize revenues, maximize profits, while minimizing risk. Just a couple of words about Aemcolo and what the future of Aemcolo is bringing beyond just travelers' diarrhea.
Obviously, travelers' diarrhea is the one that's approved, but we're continuing development in other indications as well. This includes IBS-D here in Europe. But also to hepatic encephalopathy, SIBO, and diverticulitis in the U.S. Obviously, these are three areas of high unmet medical need we feel can add additional value to the product as we continue to expand out the market and build upon the success that we'll have within travelers' diarrhea. A few words about Aemcolo and how it's very well suited for travelers' diarrhea. Starting at the top, non-systemic and minimally absorbed. This has a direct impact on something that's seen as very important, not only on the part of prescribing physicians, but also on the part of the travelers, and that has to do with antibiotic resistance.
The fact that we have a very reliable safety profile is also very important, again, both at the level of the treating physicians and the travelers themselves, insofar as looking at side effects like tendon rupture, like peripheral neuropathy, when you're talking about Cipro, having to think about what medications you might have to adjust, such as warfarin in the case of rifaximin. These are considerations that people don't necessarily want to have on the top of mind when they're on vacation. Lastly, the simple BID dosing.
Again, if you're thinking about oncology products, maybe twice a day versus three times a day isn't that big a deal, but when you're thinking about the actual use of this medication where it is going to be used, chances are, whether it's a business traveler or somebody on vacation, having the added convenience of only once in the morning and once in the evening actually does have a practical advantage. All those features that I mentioned about how well-suited it is for travelers' diarrhea have not gone unnoticed. Okay? Aemcolo is the only product that's mentioned by name in guidelines by the International Society of Travel Medicine.
In this particular guidance that's been put out, it's talking about the benefits of being prepared, of having the antibiotic with you so that you have something of known quality in your bag ready to go, should you actually get travelers' diarrhea. In our particular case, talks about the efficacy of Aemcolo against multi-drug resistant strains of bacteria. When the FDA approved the product, they put out a press release. For us, we were very happy with that because alongside the endorsement quality of the quotes that they actually put in, talking about the importance of travelers' diarrhea, as well as the importance of Aemcolo coming to market as a new treatment for travelers' diarrhea, they also flagged for us something that caused us to reflect and to think.
That was the actual number of travelers that were out there, the actual number that were at risk of getting travelers' diarrhea on a yearly basis, which then led us to reflect upon this question. Conventional wisdom would say that travelers' diarrhea is a relatively small market. If you go to the Mayo Clinic website, they talk about it being an inconvenience. If you think about the average course of, I guess, or the average set of travelers' diarrhea, it can clear on its own. To reflect from the perspective of the treating physician, it doesn't seem like that big a deal. From pharmaceutical executives that are used to big unmet medical needs, prescribers, et cetera, doesn't seem like that big a deal. However, travelers' diarrhea is in fact two words. Everybody's focusing on the fact that it's diarrhea. Diarrhea is an illness.
Diarrhea has a patient. Diarrhea has a physician. In order to actually treat diarrhea, you need to have diarrhea in the first place. Travelers' diarrhea is also travelers. Okay? Travelers have a very different definition of what inconvenience is. A doctor may sit there and go, "Well, it kind of clears in three to five days." If he has to sit on the toilet for three to five days, it's not that big a deal. Okay? If you're on vacation, a honeymoon, a business trip, big presentation, being tethered to your toilet for three to five days or up to seven is actually a fairly big deal.
In thinking about this from the perspective of the traveler, therefore how you can change the way that you position the product away from a disease with a patient towards a traveler with an unmet need, is how we're going to look at attacking Aemcolo in the U.S., or how we are going to be attacking Aemcolo in the U.S. The first thing to think about is the scale of what it is we're talking about. Okay? Even though I look and I strut around like I'm an American, I'm actually from Canada, so I did put up the population of Canada there just to give a little bit of perspective. There's 46 million people traveling from the U.S. to developing countries that are at high risk or medium risk of getting travelers' diarrhea each year.
That's an absolutely huge number. Help that sink in. If you only have 10% penetration within that group, that's still a larger number than the entire number of people with IBD in the U.S. We are talking about very large numbers here. How to-
Sorry, Sean. Can you go back? This is very important because as you can see, the IBD market, we are familiar with the IBD market because IBD was the disease at the market where we develop our technology, mainly the Uceris and Lialda. The entire U.S. population in IBD are 3 million. 15 times smaller than the entire travel diarrhea market. Thank you.
Okay. Obviously, you don't target 46 million people at once. You got to think about how it is that you're going to do this. Coming at this from the perspective of targeting a traveler versus targeting a patient who already has diarrhea is very different. Okay? The average traveler doesn't actually seek out medical advice before they go on holiday. All right? The average traveler isn't necessarily thinking about this when they're making their plans and what restaurants they want to visit or what tours they want to go on. What needs to happen is actually figure out what it is that travelers are doing and be able to target them with your marketing campaign while they're making their plans.
Also too, if this is particularly onerous to get, that last 4 to 6 weeks when people are actually starting to really get into their planning phase and picking what they're going to be doing, if you add stress to that, then you're actually going to have a lot of drop off. A lot of people are just not going to bother going forward with it. You actually have to make it easy to access this product as well. I wouldn't be fulfilling the caricature of an over-enthusiastic North American without repeating the same word in bold many times. This is really to drive home, again, the scale of this opportunity and to draw attention to what it is these travelers are actually doing.
In the top box, we're talking about the number of minutes that are being spent on online travel and digital travel content. This includes the online travel agencies or OTAs. This also includes planning for tours, looking for information around travel, et cetera, but it's a huge growth area. Already it's very big, but it's also a huge growth area and continuing. What you're actually seeing is that the shift in the U.S. towards more people booking travel online than through traditional means. Okay? Also, the statistic at the bottom, one-third of people are seeking health advice before they leave. By health advice, I don't mean necessarily visiting their doctor. They might be going online to learn about what they should be worried about in that local country. They could be going to their doctor, that could be their own prescribing physician.
That could be a traveler's clinic. They might be learning about what OTCs they want to bring with them. They might be actually getting travelers vaccines. Essentially, part of that population is already very active in trying to learn what it is they need to know in order to protect themselves from a health perspective, and also paying out of pocket. Travelers vaccines are not covered by most insurance plans in the U.S., and they can cost upwards of $150, $200, right up to $400 depending on exactly where you're going, and what the traveler's vaccine is that you require. Just to summarize here, okay? Fact one, it's huge. 46 million Americans. Very large numbers that we're dealing with. Over a third of those are seeking health advice prior to departing.
They're taking an active role in that final four to six weeks before their trip to learn all that they can about what it is they need to know in order to protect their health. They're paying out of pocket for travel vaccines. That's something we know. They're also paying out of pocket for OTCs. The International Society of Travel Medicine has actually recommended traveling with an antibiotic for self-treatment. Okay? These are three things that come together as we start to think about exactly how it is that we attack this market and what messages we should be coming up with. One of those key messages is traveler's diarrhea actually should be taken seriously. There's two key points here. One, coming back to that idea of the relative perspective on inconvenience. Okay?
You can get a very sudden onset of symptoms, and that can actually last in between three to seven days on average. It can last longer. Okay? In some cases, left untreated, those symptoms can actually persist upon your return. Very importantly for the positioning of Aemcolo within the mind of the traveler, we're actually selling a cure. Okay? If you just treat the symptoms, this goes untreated, you can actually have complications downstream after you're actually home. By selling a cure and eradicating the disease, the cause of that diarrhea in the first place, is a very important feature of our product and for the positioning with the travelers. Also, two, we mentioned the ISTM, but they're not alone. The CDC has also made these types of recommendations, as well as the American College of Gastroenterology.
We're in good company when it comes to KOLs, as well as gastroenterologists and other specialists in travelers diarrhea, family physicians that actually have taken a look across the spectrum and said, "You know what? Bringing an antibiotic with you, being prepared, thinking about this in advance, is a very important feature if you travel to large swaths of the world." To come back to it, travelers diarrhea, whether you're going for your big presentation or you're going on your family holiday, it can be a huge disruption. Okay? That, again, that relative perspective on inconvenience. Travelers diarrhea is both diarrhea, but also about travelers. When you put the traveler back into it, and you come at it from their perspective, okay, they do not want their vacation ruined. They do not want to be on a toilet for a week.
They would like to have an option for that not to happen. Aemcolo can cure you in 24 hours. That's the message. That's the message we're going with. Now, ultimately, what does that mean? In diarrhea, you're selling a treatment for a condition that already exists. Here, we are providing them with the means, the insurance of preventing that seven-day holiday on the toilet. Actually having something that will allow them to get back the activities that they desire to do, and the reason why they went traveling in the first place. Again, not like we're going to be selling a policy next to AIG or anything like that. When we're saying insurance here, it's very specific for our product in travelers' diarrhea, but we are not selling the treatment. We're not focused on the diarrhea.
We're focused on the traveler and the insurance that they bring with them. How do we do that? How do we bring that together into a succinct model that achieves everything we just talked about? Getting the message across in a successful way, out to a sufficient number of travelers, and then providing them with a very easy way of sourcing this product. Because again, this is a prescription product. It is a prescription antibiotic. What we did was, we took a look at the best way of informing as large a population as possible about the benefits of the product, the seriousness of the disease, and that would be through direct-to-consumer marketing. This is a very common practice in the United States. Many of you are familiar with it.
Direct-to-consumer marketing with the right targeting and with the right messaging, as well as very limited HCP, healthcare practitioner targeting in the beginning, but driving then those individuals to our website. The Aemcolo website would be a very standard, very traditional branded website for a pharmaceutical product in the United States. They would get information on the condition, they would get information on the product, but there would be one very clear difference from what people are used to seeing, and that would be a little button on the bottom that says, "Is Aemcolo right for you?" On which they can click, and that will move them to our telemedicine partner.
Telemedicine, I'll speak a little bit more about that in a second, but for those who are not that familiar with it's a way for an individual to engage online with a treating physician through a variety of different technological means, depending on the state. But essentially, by visiting our telemedicine partner, that traveler can then engage directly with a prescribing physician, have that consultation. An electronic health record does get created. Ultimately, if that physician deems that Aemcolo is the right product for this particular individual, there will be an electronic prescription that's sent to a pharmacy, and that pharmacy then delivers that prescription directly to the traveler's home. That total of the steps can happen less than 24 hours. Again, the majority of the planning is happening within four to six weeks.
If people procrastinate and leave it to the last minute, the model is designed to be able to actually be extremely convenient and deliver that very rapidly to a traveler who wants it. It's one thing to put up a pretty diagram about how it's going to work. It's quite another to make sure that the execution is going to be flawless. It's important to make sure that you're operating and working with the appropriate people. Alex spoke a little bit about the evolution of the team in the U.S., but that team very much remains a group that has a very strong commercial presence with direct experience in gastroenterology, understands the product very well. Strong links with the KOL community, particularly those that are making the endorsements in the ISTM.
They have consumer health as well as digital marketing experience, which obviously is very important for this type of model. They're really the team that's driving then our partners in this, which are Ogilvy Health, a very strong marketing firm. These are the people that are helping us then tailor the messages as well as tailor the targeting for those travelers as a first step. They have direct experience in travelers' health, as well as using telemedicine with other products within their client list. The telemedicine partner is a group called UpScript Health. Now, the benefits for us of working with UpScript is here's an organization that's actually been in existence for over 18 years.
They already have a variety of different clients. Also too, for those of you who are familiar with the telemedicine space in the U.S., you might usually think of some of the bigger players like an MDLIVE or a Teladoc, who only deal with the telemedicine itself. UpScript actually has telemedicine as well as their own pharmacy. They can act as an end-to-end for us, as well as a little bit of a closed-loop system, to be able to actually manage the physician consultation, the delivery of the electronic prescription, as well as then the actual dispensing of the medication and home delivery. I guess to set everybody's minds at ease that this business model isn't a result of legal cannabis in Canada. Okay. We're not alone in thinking about this in this way. All right?
This is a trend that's been happening in the pharmaceutical industry for a while. Big pharma has been hiring on chief digital officers. Okay? Health records are already highly penetrated into the U.S. market. Over 80% and over 90% in some hospitals.
We have rats in the room. No. We have no rats here. No. There are no rats here.
Oh, okay. Electronic prescriptions with Surescripts and others, electronic prescriptions are already above 98% penetration in the U.S. What we're really doing is leveraging technologies that already exist and actually are already utilized this way, just in other therapeutic areas. For instance, Roman.com, Hims.com In men's health, Nurx in women's health. We're now actually coming at it with a new brand and in travelers' diarrhea, very much following a path that others have trod before. That's the important thing here, is we aren't necessarily reinventing a wheel. We're actually combining different parts that are already well-established and available for us and just putting it towards a new application when we're talking about Aemcolo. As I mentioned, we're not alone here.
There's a lot of companies right now, a lot of companies of various sizes that are trying to crack this particular nut, figure out how it is that they can utilize these technologies that do exist. We're really just at the forefront by bringing this together for this type of product in this therapeutic area. What are the benefits? Ultimately, there's a more straightforward sales and distribution. I guess benefit number 1 is we get to attack a much larger market opportunity. What it does allow is a more straightforward sales and distribution model.
Alex had mentioned that this gets rid of the need for what you would normally associate with diarrhea, a disease, physicians, physician detailing, and in that particular case, a relatively large sales force to be able to actually address the number of physicians that would be required in order to really go about that in a much more traditional fashion. Also, two, it reduces the complexity of our whole distribution network from the number of wholesalers in the distribution chain right down to pharmacy dispensing. The model itself being digital as well as the scalability of our partners allow us to address the market, but still within that closed-loop system. Marketing directly to the traveler. On the previous slide, there was one little or two slides prior, the forget thinking about the patient pharma shifting to consumer-centric marketing model.
As a matter of fact, the whole rise of telemedicine in the U.S. is based upon this let's get rid of that supply side control, the physician controlling when they're available, where you have to have this actual online consultation. Telemedicine has grown because of that drive in the U.S. towards more of a consumer, customer-oriented type of mentality when it comes time to health delivery. It's not about patient and illness, it's about individuals and wellness. That's a trend that's been happening for a while, and that's certainly something that we are able to capitalize on and for this particular product opportunity. KOLs are still very important stakeholders for us, however, because they feature prominently directly in that our ability to position this as something that has been vetted and is recommended by those individuals for the travelers.
Lastly, another important feature of this model, if you imagine starting with your digital marketing going all the way through and being able to track that individual all the way through to the home delivery of a product, there's going to be multiple points where that individual may continue or may fall off. We're able to actually track this on an individual by individual basis, see where they fall off, and be able to tweak the marketing campaigns as well as tweak the process accordingly to reduce then what those fallout rates are going to be. Often when you're talking about a product launch, there's not necessarily that seamless integration from end to end, you actually will kind of lose off. Well, yeah, okay, this is how we're measuring the metrics for our marketing campaign and what we think it's resonating.
When it goes into that distribution network, that wholesaler network, and ultimately to the end pharmacy, you lose that ability to know just how well that's translating into a sale. We have that directly with the model that we've set up here, therefore, can utilize that information to come back. Obviously, that information will be very valuable for us as we expand out, not only in this particular indication should we choose to start seeing some of those specialist traveler clinics, et cetera, but obviously in other indications as well, and expand out our activities to include physician detailing. Contextualizing these numbers. The American Association of Retired Persons put out a survey about traveling habits in the U.S.
What you can kind of see is at the top, got millennials spending about $4,800 out of pocket each year on travel, down to the baby boomers spending just over $6,300. I think it's important. This statement is important from a contextual standpoint because we have a lot of Europeans in this room who are used to maybe four to six weeks of holiday per year. In the U.S., this is actually around one to two weeks of holiday per year. Out of pocket, when you start looking at one to two weeks of holiday, this becomes a very significant amount of money that they're paying. Again, thinking about what they're already dispensing or disbursing for travelers vaccines, well, why would somebody pay $400 out of pocket?
Well, it's for this exact reason, because they want to avoid getting sick on their holiday. They want to avoid having something happen. When we come out, our plan is to come out around EUR 150, then it fits very much within the range, as well as when thinking about the insurance to avoid kind of not being able to fully capitalize on the investment you're making. We feel it's a very appropriate price point to come out at, as well as we have then the closed loop network to be able to feed back in and help us decide exactly how we're going to price that product on a going forward basis as well. I think just in terms of summarizing, pretty sure this is my last slide. Travelers' diarrhea. Diarrhea is a disease. You have a patient, you have a doctor.
Travelers are worried about not being able to fully capitalize on the expense that they're making, about losing out on that quality time with families, about missing that big presentation in front of the company. Okay. These are the things, these are the reasons why they're traveling in the first place. The inconvenience of being tethered to a toilet bowl for three to seven days is enough to call them to action. Coming up with the right messaging in order to do so, how to position, raise the awareness of what the condition is, the seriousness of the condition, what the options are for it, and what the best options are, then providing them with an easy way of accessing it, is what we're doing with this model, and what we feel is going to help us to be a success in the U.S. with Aemcolo. Thank you.
Okay. Is this working? Yeah. Thank you. Now we will be telling you something about our very latest entry in our pipeline. This is something that will be taken care of, as I said, by Mara Girolami, the CSO of Bellatrix. We have invited Professor Michele Maio, who's the director of the Immuno-Oncology Center of the University of Siena, to introduce a little bit the background around the current situation in oncological product development. It's important that one understand what is the situation around the oncology drugs development to understand what we're trying to do with our new product. Thank you, Professor.
Okay. Thank you. Thanks a lot for the invitation. I must say, I'm quite happy to be here because as the chair said, I'm the chair of the Department of Immunotherapy at the University Hospital of Siena. Immunotherapy, as you know, has dramatically changed in the last few years, the treatment of cancer or some types of cancers. Being very chauvinist in terms of what the powerful and the potential of immunotherapy is, I'm also a little bit sorry to say that there is still a huge unmet medical need in cancer, mainly in some indications in which we need new drugs and also new therapeutic approaches. For sure, in the last 10 years, there has been a dramatic change anyway in the scenario of cancer treatment. This, of course, has been due mainly to two factors.
On one side, the improved knowledge on how cancer works, develops, metastasizes, and also in some ways, how it does interact with the immune system, but also what are the receptors that we can target on cancer cells in order to improve the efficacy of our daily practice in the clinic. On the other side, we have also learned a lot in terms of new drugs that are under development that have a strong potential to further improve our ability to treat cancer patients. As you can see from this slide, of course, it is a busy slide. I don't want to go through any of the details of this slide, but there has been a large number, a very large number I would say, of new medicines, new therapeutic tools that have been approved in just a few years in different tumor types all around the world.
What has dramatically changed actually in the last few years, I would not even say in the last two decades, in the last few years, that the time to market of a number of drugs has shrunk dramatically. There is much less time from initial phase, these studies, to having this drug available in the clinic. This is, of course, mainly due to the unmet medical need and also due to the, of course, the activity of these drugs that in some cases have been approved only based on single studies, phase II studies, in some cases even first phase I studies and single trials. This has, of course, dramatically reduced the time to market, has dramatically reduced also somehow the investment that you have to do in order not to go through phase I, phase II, phase III, confirmatory trials, and so on.
Part of this concept, again, this is a quite busy slide, is summarized here, and it clearly demonstrates that there are 2 major categories of agents that are under development and that have been launched. The immuno-oncology drugs and also all the other, let's say, the non-immuno-oncology drugs. Both these type of approaches have led to the approval, also from very initial clinical trials of drugs that are on the market for different indications. Who is developing those drugs? Not necessarily, I would say, and I agree with the content of this slide, of course, not necessarily big pharma, but mainly, mostly the biological drugs, the target drugs, are mainly developed by small companies that then are partnered or acquired by bigger pharma in order to further develop the products they have in today's pipeline. This is clearly shown in this specific situation here in this specific slide.
When you see the small green dots, they identify small companies that are developing oncology drugs, that have oncology drugs in their pipeline, one or more oncology drugs in their pipeline. The big bubbles, the big blue bubbles and the big green bubbles, are mainly from big pharmas. Those are the companies that acquire the agents that have been tested even in phase I clinical trials in order to further develop the product. Probably they do it in a faster way, in a more organized way, and in a more powerful way as compared to small pharmas. I'm saying this as a general concept. As I said before, there are 2 major categories of therapeutic agents in which there is interest by the scientific community, the academic community, patients, of course, and also from the side of companies.
Those are not only biologicals. When I say biologicals, I also mean, of course, the whole world of immunotherapeutic drugs. There are, in the last few years, a number of biologic drugs in late stage development has tripled. These are non-immunotherapy drugs. This number of small molecules has also increased significantly. What is changing in the field of cancer treatment is that chemotherapy, as you see from this sentence, chemotherapy is not where the, let's say, the scientific world, the development of new drugs is going.
In fact, this is much well represented in this slide, in which in the right part of this panel, you can clearly see that in terms of cytotoxics in the last 10 years, practically, from 2007, 2017, the number of cytotoxics, and the percentage, better the percentage really to make the point, has practically decreased by 50%. That means chemotherapy is not what the whole world of people who are involved in cancer treatment believe will be the future. On the other side, when you see the targeted molecules, targeted molecules have grown from 254 to 335, and the percentage is still a fair percentage. This is a field of investment. This is a field in which we should focus our attention.
Of course, in addition to the targeted biologicals that have tripled in terms of absolute number from 95 to 301 in the last 10 years. This, of course, has been the huge development that there has been in terms of having available new molecules, and when it's written targeted biologicals, is mainly meaning immuno-oncology and immunotherapy drugs. Basically, there are two areas, targeted therapy and biologic therapy or immunotherapy better, that are the leading areas in which the field believes that in the next few years, we have to concentrate our attention for the benefit of patients. In fact, if we look at the situation now, what happens in the daily practice, immunotherapy has certainly represented, as I said, the most rapid and powerful advancement in the last few years for cancer treatments.
Still, there is only a limited percentage of patients that are treated with immunotherapy drugs. Perhaps we can have discussion about the efficacy later on, this is not the purpose of my presentation. This is clearly depicted in this slide. This is the proportion of cancer patients among 150,000 patients that have been treated with antibodies directed to PD-1 or PD-L1. Those are two inhibitory checkpoints in which there are drugs that have become available in the very last few years. If you see, of course, in 2017, on this right part of the slide, a large proportion of lung cancer patients, melanoma patients, kidney, head and neck patients have been treated with this type of approach. This is normal because we have drugs that have been approved and that have demonstrated a large superiority as compared mainly to chemotherapy.
There are other tumor types, the smaller percentage here, this 12.4% of tumor types, which are, in some cases, more rare tumor types or rare tumor types, in which there is still a huge and very large unmet medical need because we don't have medications that are effective in this patient population. Just to give you the flavor of what happens in the clinic when we use these drugs. If you look just simply at the red curve, this is practically the survival of metastatic melanoma patients that has clearly dramatically increased due to the availability of drugs that modulate the immune system. This curve was flat until a few years ago, very few years ago, because we had only chemotherapy that did not have any effect on the survival of metastatic melanoma patients.
In this case, there are two major drugs or two major categories of drugs that are improving significantly the survival of melanoma patients, immunotherapy on one side and targeted therapy on the other side. Again, it's not only immunotherapy, but it's also other agents that work exactly in the same direction in terms of improving the effectiveness or the survival of advanced melanoma patients. If you see the bottom lines, those are flat. Means there are a number of tumor types, those are just a few examples, that really represent an unmet medical need, because in the past few years, since the 1970s, there has been practically no improvement in the survival of these patients. Means we need drugs that we can utilize effectively in the clinic to improve the survival of patients affected by a number of tumor types.
Just to give you an idea of which could be some of the major areas of interest for the development of new drugs. Some examples of unmet medical need is triple-negative breast cancer. Triple-negative breast cancer accounts for about 5%-6% of all breast cancer patients. Is a huge unmet medical need because there is nothing that works in these patients. We cannot use hormone therapy. We will not use immunotherapy. Chemotherapy is the only strategy that we have. Again, when we go to the other two examples like hormone refractory or castration-resistant prostate cancer, stage 4 colorectal cancer, in this case, we are speaking about big killers. We are speaking about two of the four considered big killers.
Means that for a huge number of patients that are affected by these two types of diseases, we still don't have effective treatment in terms of improving their survival. There are also other tumor types in which there is an unmet medical need, like for example, pancreatic cancer. In pancreatic cancer, we know that, for example, immunotherapy doesn't work. Patients with pancreatic cancer are a major problem for us also as clinicians, of course, because these patients, they have a progression-free survival that really accounts for very few months. These patients die in less than a year, practically. You can clearly imagine that not having any perspective also, for example, with immunotherapy in pancreatic cancer, how important it is to have something new in these type of diseases.
I hope I've given you a very brief introduction of what is ongoing in the field of cancer immunotherapy. Just to summarize a few key points. For sure, we are also as clinicians or as scientists, we are living in a fantastic moment because for some diseases, we have drugs that work and that improve the survival of our patients. In addition, the whole mechanism, the whole field has become much faster. Until a few years ago, it would take 10 years from the beginning of treatment, the beginning of use first in human, the clinical trials of a drug, and the registration of that drug in case the studies were positive. Now, I've shown you the PD-1 antibodies. Just for those of you that are not familiar with these antibodies, one of these agents has been utilized in humans for the first time in 2012.
The first approval of that specific agent was in 2015. Two years to go from the bench to the market. The other concept, more in general, but you are much more expert than me, is that small companies are the ones that are really the engine of what is happening in cancer treatment because they have more flexibility, because they have more speediness in the interaction also with the academic institutions. Those are the reservoir of ideas of new and promising therapeutic strategies. As I showed also, chemotherapy is going down. Targeted therapy is slightly, but it's increasing. Biologicals, more in general, has definitely increased.
I think that from my last slide, I've clearly shown you as a clinician in this case, that we have some tumor types for which we desperately need new medications, either in clinical trials or, and hopefully soon after, on the market. Thank you very much.
Ce la farai così veloce.
Thank you to Professor Maio for the great introduction. I am Mara Girolami, I'm a PhD, Chief Scientific Officer of Bellatrix Therapeutics, which is a subsidiary of Cosmo Pharmaceuticals. I was given the opportunity to screen a library of small drug compound from Cosmo Pharmaceuticals and select two of them. One is CB-03-01 that is being developed in the dermatology arena for the treatment of acne and alopecia, and another one, CB-03-10, for the treatment of solid tumor. What did we do at Bellatrix Therapeutics? At Bellatrix Therapeutics, we selected CB-03-10 and put it in vitro. Let's see if I can find the pointer. And put it in vitro in the Sorry. Oh.
Now you have to fast forward for us, like, 70 times.
Yeah, exactly. Entertaining. Anyway, we put it in vitro in. I was looking for the pointer.
No, it's okay.
In contact with the several cancer cell line in order to determine if they were sensitive to the small drug. We selected androgen-resistant prostate cancer, pancreatic cancer, colon cancer, and triple-negative breast cancer. As Professor Maio illustrated earlier, they are high unmet medical need cancer. We were able to define that CB-03-10 is active on all these cancer cell line where they have been exposed in vitro to the small molecule. I highlighted in blue the one that then we took. These are human tumor that have been implanted in mouse, and then these mouse have been administered orally with the small compound. On the right side, you can see a represented diagram of one of these animal model, where you can see that it's active. In blue, it's very active when a human tumor is implanted in the mouse versus the control, which is the black one.
You can see that there is the reduction of the diameter of the tumor in the animal that has been implanted with the tumor, assessing the efficacy in vivo in an animal tumor of the small molecule. In red, you can see that we compare our compound, the CB-03-10, with enzalutamide. enzalutamide is a new product that has been developed for the treatment of castration-resistant prostate cancer and has been in the market, and it is the standard of care for this treatment of these tumors. In our case, CB-03-10 has been more potent than enzalutamide, and this is only one representation. We did the same for pancreatic tumor, put it in comparison with the standard of care for pancreatic tumor, which is gemcitabine, CB-03-10 consistently is more active in the animal model as well as for triple-negative breast cancer.
At this point in our end, we had a product which is in vitro very active on cancer cell line of various origins, again, pancreas, colon, and prostate cancer. It works in vivo in the animals on human cancer. At this point, we also determine that it's more potent than enzalutamide in this type of cancer. We also created a tumor that is resistant to enzalutamide because there is a subpopulation of people that are treated for prostate cancer that became resistant to this enzalutamide. We are not talking about a small population, but is 30% of the population. We were able to show that our compound is also active on this population that is resistant to enzalutamide.
At this point, we decided to perform a series of safety test because in order to develop a product, you don't have only to show that it's good, that it kills cancer in vivo or in vitro, but you have also to show that it's safe. Otherwise, the FDA or any other regulatory agency is not going to give you a green light to proceed for testing in human. After we show that this is a very potent antitumor agent, we were also able to determine that it is safe after oral administration in the animals model. We put together all these results, we submit it to the FDA on what is called an IND.
In 30 days, we got cleared by the FDA to proceed and treat the first human, with not really question on any clarification of what we submitted. So our purpose is proceed and start to treat a patient in a phase I clinical trial. Phase I clinical trial is usually in order to determine which is the right dose in order to proceed in the human, and this is going to be the part one, where we're going to do escalation doses in a patient in order to determine the optimal dose, which is going to be safe. Meaning, is not going to give very serious side effect in human, but is going also to give us some indication about the efficacy of the treatment.
When we are going to find the right dose, we're going to proceed and treat a smaller cohort, we think around 60 patients, in order to determine if our compound is also efficacious in the treatment of a specific tumor. So there is the plan for CB-03-10 after this initial testing in human to license after the phase I clinical trial. Why could be of high interest for a company in order to acquire? Because as Professor Maio illustrated before, there is a high interest in therapy of solid tumor, particularly tumor like pancreatic cancer, which has a survival rate around between 5%-8%. Is also defined as an orphan drug, meanings that you can have accelerated approval, sometimes even with some few population of people, like 60 people in a phase II, you can go directly to market.
There is colorectal cancer, where our compound, again, has been proven very active. That is still the second leading cause of cancer between women and men in U.S. Again, we receive interest from licensing partner because, again, there is high interest in pancreatic and also in that population that I illustrated you before. Are these castration-resistant prostate cancer, where they are submitted to enzalutamide or any other androgen receptor treatment. However, there is 30% of the population that in six months change the target, so they became resistant of that treatment. If they become resistant, that means that they are going to die in a short time, usually six to 12 months. This is going to be another good target for our therapies.
CB-03-10 is of high interest to big pharma as a license candidate because of a very strong potential for first and second-line therapy in solid tumor. Between these tumor, there is pancreatic, colon, and certain subtype of prostate cancer that became resistant to conventional therapy, and all these cancer share poor prognosis and high unmet therapeutic need. This is a summary. CB-03-10 is a small molecule, which is going to be administered orally in patient. The target are androgen receptor and glucocorticoid receptor. It shows an impressive anti-tumor activity, again, in vitro and in vivo. It has a potential for first and second-line therapy in pancreatic colon and prostate cancer and other cancer. There is a regulatory toxicology that shows that oral dosing is safe and well-tolerated, which is an important thing. IND has been approved in 30 days without any revision by FDA.
We are planning to start to treat the first patient in the phase I clinical trial at the beginning of the fourth quarter of 2019. Again, we have potential licensing partner that are looking to execute the deal and acquire this compound that has a very high potential in the small molecule oncology arena.
Thank you.
Was I quick enough?
Thanks to all the speakers. The good news is that we're about to close. The bad news, which I've learned only a couple of days ago, is that we have to free this hall around 5:30, which means that there's not going to be a lot of time for questions. I can wrap up very
Because of what, Adam?
I don't know because of what. I think that they're probably having another event. We didn't know this, so we have also booked the upstairs hall for our reception. But it's unfortunate that we have to leave the room by 5:30. I hope that we have been able to convey to you that Cosmo, yes, it's a small organization, but really works relentlessly. I don't think that any of these that you have seen here would have been possible without the hard work of a lot of people that you don't see frequently here speaking. I remember recently I spoke with an investor that said, "Well, but we always meet the very same people in the presentation. It would be good to understand what's really behind." I can tell you the following, that there's a lot of people behind.
I have a list here, the list that I have here is just the list of the people that are present today of the Cosmo organization, that some of you may wish to maybe talk to in the next hour or so during the reception. All this has been made possible because of the people that do the work, but the people that you don't see, to which I am personally thankful. I'm just going to list the people that are present here, so those that are not will need to excuse me because I cannot really mention everyone. The people that we have here in our room, and they are just listed in alphabetical order. Here you have Luisa Bartorelli, our Chief Patent Counsel. We have Roberto Camerini, our Deputy CSO. You have Andrea Cherubini, the head of the Artificial Intelligence unit.
You have Giuseppe Cipriano, our Chief Operating Officer. You have Michele Ferrara, who's the manager at Linkverse. You have Enrico Fremonti, who's a pharmaceutical development manager at Cosmo S.p.A. You have Marco Lecchi, who's our head of internal audit. You have Luigi Longo, who's a scientific project manager. Andrea Lovati, our quality assurance manager. Cristina Macelloni, another pharmaceutical development manager. Davide Malavasi, our qualified person and technical director of our plant. Alessandro Mazzetti, our Chief Medical Officer. Fabio Merlini, our corporate IT manager. Gian Paolo Montalto, our business analyst. Luigi Moro, whom all of you probably know already, our Chief Scientific Officer. Nhan, the head of R&D for the Cosmo AI. Massimo Pedrani, the head of generic business development. Giulia Ruffino, our communication designer. Roberto Villa, our manufacturing officer.
Again, to all these people and to all those that I've not listed, our personal thanks for the hard work that's been done. Sorry, I don't think I've listed Niall Donnelly, our Chief Operating Officer, and also Kevin Donovan, our board member of Cosmo Pharmaceuticals, indeed, that are also present today. Cosmo has a consistent and diversified pipeline in different stages of development. I really need to stress what Mauro is always saying. There is no model that can actually capture us efficiently. We're sorry about that, but this is the reality.
We have no model. We know what Cosmo really is. Just to give you, I started in the meeting saying that never give up, never arrogant. We know, for example, in the oncology pipeline and product that. There is a limited role that we can play. It is a role that I strong believe that is a creation of value for the company, but we know since now, since scratch, that is very important at the end to partner with the right partner. What I can say you is that we already raised a lot of interest by big pharma because as Professor Maio said, in the research and development in cancer, looks like in the last two decades that the DNA of the small company is, let me say, better. Better because they can move faster, they can move quicker.
At the end of the day, we are not intent to establish an oncology company. I have to thanks Mara, because Mara, even though is one of our employee, works with us the last 20 years. Thank you, Mara. She lives in San Diego. She has a very strong sense of belongings. That is something that only with this you can build, create a company. Mara forced me just to develop something far from the dermatologic market. Let me say that at the end, I have to thank you, Mara, because will be one of the major protagonists in creation of value, I hope, in such very important development.
I was just looking at the list, I am not sure.
It's not important
another very important person here in the room who's Roberto Villa, actually.
That is Sorry, Roberto Villa. Stand up, Roberto Villa.
Roberto Villa.
Roberto Villa is.
Is one of the founder.
Roberto Villa is the guy.
Roberto Villa is one of.
Roberto Villa is the guy that's Roberto, I know that you are old, but please stand up just. Roberto is the guy that's founded the company with me, is the founder of Cosmo, and thank you, Roberto.
Sorry. It's terrible when you have those lists and all of a sudden you think that you've missed someone, but maybe it was better like this. We have a consistent and diversified pipeline in different stages of development. Four products are already in the market. One new product will enter soon. We're talking about the artificial intelligence that I don't think has been factored up as of today in any way or form in our shares. As I tried to explain before, we have a net cash of €348 million, which is close to 400 million Swiss francs, and we believe that it's net for the reason that I've explained before.
Our convertible financing was raised to build up the commercial infrastructure in the U.S. and the scale-up of the AI business is now simply not necessary after the deal with Medtronic, which we wouldn't have expected at onset that would have come at such good terms. The cash that therefore we have available simply increases our firepower. Our intention is just to go ahead, full throttle and ready to capture whatever additional opportunity may present itself. I would finish our presentation.
Maybe, sorry, maybe it was not clear. We are ready to launch Aemcolo. The launch of Aemcolo will be in the third quarter of this year.
Yeah. It should be in a window between the end of June and mid-July. This is the moment in which we expect to launch. We're happy to open up now the Q&A session. If there's any question, please go ahead. You raised your hand first. You need the microphone. Do we have a microphone for
I have the mic.
No, no. There's another one. I guess. There's no other microphone?
I can speak up.
No, wait. Let me pass you the microphone. It's better, Mauro.
Okay.
Please.
I'm impressed by this white box over there of this artificial intelligence. Why do you still need Methylene Blue if you have this box?
I don't see it.
This is very simple. Mauro, you want to answer the question? You want to answer? Sorry, we have only one microphone.
It's very simple. I can explain you why. Unfortunately, we are not approved, but what we are doing now is, in this kind of segment of business, you cannot stop, never. You have always to develop something new. We already develop something that is familiar with the company, because thanks to the Methylene Blue MMX, you can see more, you can see better, and you can have major opportunity to reach our goal that is a better diagnosis in the IBD, in the dysplasia. You have to take in consideration two factors. One is that IBD is familiar with us. We are a leader in the IBD in the U.S. Second, if you talk with gastroenterologist, they say that 50% of the diagnosis of the IBD is wrong. You have to take in consideration that for IBD, under the name of IBD, there are two main diseases.
One is Ulcerative Colitis, the other is Morbus Crohn. For Ulcerative Colitis, there is no doubt that is along the colon, is not in the ileal part, but is along the colon. For the Crohn, there is major difficulty to assess the right diagnosis because it's along the colon, exactly like the Ulcerative Colitis. There is a very strong difference in terms of treatment. I give you the example. In the Crohn, the antibody works very well, and the Ulcerative Colitis are no result. The result are very poor, even less than the normal anti-inflammatory. Means that a better diagnosis can be in favor of the patient, in favor of the community, because in the major of the cases, they are using antibody that is 20 times costly than normal anti-inflammatory with no result. This is thanks to the Methylene Blue MMX.
Our friends that are sitting exactly there, they are hardworking and setting, thanks to the Methylene Blue MMX and the artificial intelligence, a new, correct, let me say correct, diagnosis for the IBD. It's one of the cases. I can tell you. I can tell 10 other examples. Methylene Blue MMX is still alive in our company. We are exactly after Christ, after the Methylene Blue MMX, but we still work in Methylene Blue MMX because we do believe that thanks to Methylene Blue MMX, we are just in this position. We are going to launch something that is really revolutionary. Thanks to Methylene Blue MMX, we could increase the revolution. Revolution cannot be stopped. Every second, every minute, we have to work hard.
Let me also tell you something in this respect, which I hope will find the agreement of our AI colleagues, because maybe there's a little misunderstanding that could be explained somehow. The artificial intelligence is called artificial because it mimics the human intelligence. It's not something different. It tries to mimic, actually. We are fortunately more intelligent than machines, otherwise the machine would create man. Instead, it's the man that creates the machine. The artificial intelligence in this context is trained to see what the human eye see. Therefore, the artificial intelligence will not be able to see something that the human eye doesn't see, simply because it is trained on what the human eye see.
if you introduce anything like a contrast agent, methylene blue, that helps to see better, that will simply help the artificial intelligence as much, because if it helps the human eye, it helps the artificial intelligence as well. I hope this explains it. Thank you. Oh, no. First, we have a question here, sorry.
Thank you. Actually, I have three questions. One is on colo. You want to launch in June, from June onwards?
Yeah, June.
What are your peak sales estimates for that? The second one would be on oncology. Do I get it correctly that it was more by fluke that you started to go into oncology?
Excuse me?
Was it more by chance that you started to
Okay, thanks.
go into oncology?
Two very different questions. You have a third, you said.
Yes. The third one is considering your Medtronic agreement. There were some questions raised about the fact that Kenneth Griffin just took a stake in Cosmo as well.
Who? Sorry.
Kenneth Griffin.
I don't know him
the owner of hedge fund Citronic,
Hedge fund. Which hedge fund?
Citadel.
Citadel, sorry. Citadel. That it's a bit of an accident that first he takes a stake, and then you have the agreement with Medtronic. Thank you.
Okay. Thank you. Well, let me answer the first question about the forecast. We're still in the process of developing appropriate models, so this is the reason why for the time being, we're not changing our guidance. Guidance continues to be for 2019, the one that we have already released. We will give-
The peak sales for oncology.
The peak sales for-
Yeah, yeah. [Foreign language] for oncology.
Oncology, there's no reason for us to change anything in respect of what we've said so far. We have projected, if I remember correctly, the peak sales, I would need to go back to another original presentation. I think peak sales were around EUR 300 million. I always said that that was conservative. The reason why we said it was EUR 300 million is simply because the competitor to whom we're constantly compared, XIFAXAN, sells EUR 1.1 billion. I simply said, why shouldn't we able to do at least 30% of what they do? You can take that as a reference, a very blunt reference, but it's not really the fruit of a detailed market analysis, which is ongoing, and that needs to be refined and perfected according to the new model that we are developing right now. The second question was, why oncology?
Like Mauro was trying to convey, it didn't happen by chance. We had started the screening of anti-androgenic compounds a lot of time ago. As Mara explained and conveyed, we had a proprietary library of compounds which we started screening quite some times ago, and this initial screening is the one that led to Winlevi and Breezula in Cassiopea. Those are anti-androgen compound. Actually, it's the same anti-androgen compound that has two different application. One in the form of cream for acne, and the other one in the form of lotion for androgenetic alopecia. As Mauro was trying to convey, we don't find ourselves right now in the oncology field simply because we have decided to invest in the development of new molecules or because we have bought a molecule for someone.
Simply, in these years in our biotech labs in La Jolla with Mara and her team, we have continued the screening of this anti-androgen compound, and we have realized that there was one CB-03-10 that had potentially very interesting activity against certain types of tumors. This is why we decided that basically it was too good of an occasion to be wasted. We know it was sort of out of focus, if you wish, but actually it was already in our pipeline and it was owned by us. It's a new chemical entities that appears to have some very promising property. Like Professor Maio explained, today the development of oncology drugs has changed very much. We don't expect that this is going to be particularly expensive, actually not at all, to conduct a phase I.
When we're going to have new and interesting activity data, that's the moment where we will partner that. We don't mean to develop it ourselves, we would like the investors to be reassured that it's not our intention to become an oncology company. In respect of the last question that you made, frankly, I don't have a clue. I don't know the person you mentioned. I'm not aware that that person has ever entered into any contact with any member of management of Cosmo.
No, I didn't say that. He bought a stake of Brisola, something around 3% in your company. I mean.
He must have bought it, I guess, in a very diluted way, because I don't think that you can buy 3% of Cosmo and without the shares going back to 200 if you buy them like this. I really don't have a clue. I suppose that he must have built up.
It's in the financial.
The position over time. I frankly don't even know who this person is. Other questions? We have Statis there first. Oh, sorry. Then Barbora.
Sorry.
Hi. Four, if I may. On the EUR 348 million you hold, I suspect, that's a question. Is there any intention to return those funds, buy back part of the convertible, or you plan to hold those funds until something appropriate arrives? On the AI price, you mentioned EUR 36,000 a year. How do you go about pricing that product? It works out roughly EUR 10 on the busy, on the full capacity colonoscopy centers. I suspect it works out single number of EUR per colonoscopy, even anything up to EUR 15, depending on
On the capacity. Third question, that's probably for Nhan, on the AI. Once you commercialize, you're going to have a lot of data. Is there any scope to automate the post-processing of this data in order to train your algo? Or you have to manually keep going picture frame by frame and doing it with a human help? The last question. Apologies, four questions. Maybe Sean could answer that. Depending on the country, there are issues on issuing antibiotics freely without having an indication of sickness. Would that be an issue? I know there's no systemic absorption.
No, I got the question.
But-
I'm cutting you short, sorry, because we don't have a lot of time.
Yeah.
I understand the question.
Yeah.
First, I'm sorry, we need to rush because it's unfortunate that we don't have time to accommodate everyone. First question, what we're going to do with the cash? Well, listen, we will see. We don't have a specific plan, but Mauro has an opinion which I completely share, that it is much better to have the cash than not have it. We will continue.
I confirm.
We will continue along those lines. Second question. The reason why we have done the deal with Medtronic is because they're supposed to be the masters of marketing and not us. We'll let them decide what's the best strategy. They will end up making a lot of money if the product is successful, I'm sure that they know what they're doing. I think that you got a very right point, if I correctly understand it, meaning that if you divide the potential cost by the number of colonoscopies that's done by each colonoscope, it will end up that the price that will be paid for the use of AI in a single colonoscopy is going to be very low. You know what? This is good news because it can increase then. Right?
I'm pretty sure that if there's going to be room for increasing, Medtronic will increase it. They will be the person responsible for the pricing. Nhan, you have to answer in a second.
Yes, absolutely. I will be very
Are you?
Yeah. Okay. I will be very short. Yes. The answer is yes. Essentially, we will be using and empowering this cycle to face the huge amount of data that is coming in.
For the antibiotics, let me say that is not true, because there are only rifaximin that is a non-systemic, very few absorption. We have no big concurrent in the antibiotics market for travel diarrhea.
Barbora, you had questions.
First.
Microphone on. Is it on? Okay.
How many people work in this AI organization? Second is, also for me, it sounds more like software, so why do you need the white box?
Use the microphone
How long do you expect the phase I study in oncology to take? Last question, did you have to pay a penalty to Olympus because you canceled the deal or because it
I'll start from the last one. No penalty. There was a mutual consent termination. Nothing had to be paid to Olympus. In respect to the first question, we currently have 10 people working in the AI. We don't expect it to ramp up very quickly, simply for the reason that we have subcontracted, in agreement with Medtronic, the assembling of the device to a very well-known company. Therefore, we don't expect that we're going to have a significant increase in employees because of AI.
Yeah. About the second question. Yes, it is basically a software, but since it has to enter in a context where there is a patient, we need to provide medical electrical equipment to stay in that area. It is not possible to install such a software with AI on standard endoscopic equipment. That is the reason for which we provided a very specific hardware, so we can provide a very plug-in product for this market.
Barbora, it is important that the market understands that the technology and the IP, it is in the software, it is not in the hardware. The hardware are highly sophisticated components, but components that you can use for many different tasks. You have very powerful processors and that kind of things, but that is not where the intellectual property resides. That resides in the software, the algorithm, and the patents. Mara.
Regarding the duration of the phase I, the first part where we are going to find the right dose to administer to the patient should take no more than six months. The second part, where we are going to treat with that dose, a specific patient population, we are thinking probably around one year. We are going to roll at least 10 clinical sites, most likely in the United States, and go as fast as we can.
Patient is not going to be a problem. Patient enrollment is not going to be a problem because we have to keep in mind that these patients don't have alternative therapies.
Okay. We had Bob. Bob was first.
Just again, congratulations on this. Another rabbit out of the hat. First, methylene blue- and now this AI device. I think it is very revolutionary. It's just like an auto-focus on a modern electronic camera. I think it will also give a run for the money for methylene blue as well. My question, what is actually the U.S. regulatory pathway? We know that's been critical also for methylene blue. Just on your IP, you mentioned you have patent protection there. Okay, it's also software, so you have probably a lot of trade secrets there as well, meaning that you can extend this probably beyond the patent protection.
Exactly. Okay. Quickly on the regulatory pathway, we're discussing this with the FDA. It's likely that they will ask us, notwithstanding the data, that we have to perform a small trial. Don't forget, we're talking about a device here. We're not talking about a drug. The pathway for devices is completely different, and this is what we're currently discussing with them. If it's anything of that kind, it's not going to be something extremely complicated, and it's not going to be something that's going to last for a long time. This is why we are envisaging on our timeline that we could be in the market in the U.S. at the beginning of 2020. In respect of the intellectual property rights on AI, you're completely right. Those are composed by basically trade secrets and patents.
Patents can protect effectively only one portion of the significant innovation that's behind the product. Therefore, you also have to rely, as you think you know better than me, you have to rely extensively on trade secrets. Please.
I have also two, three questions. One, you said the margin on the colonoscopy device would be 20%. Is that the first year when you actually also sell the device, and after it will be reduced when you only get the
No, sorry. The device is not going to be sold. The device will be bought by Medtronic, then Medtronic will place it for free into the hospital and institutions and will charge monthly for a fee. The first fee, cumulatively, on a yearly basis, is expected to be EUR 36,000.
Okay. In the production and in the selling of the device, you don't have any share or wasn't it mentioned that you also
No, we don't expect. The share that we're going to have is the share on the revenues that will be generated.
Monthly
generated monthly by Medtronic. Therefore, we expect that from what they will pay us less the cost that we expect to have, our net margin will be equal to 20% of the overall sales, of the gross sales. Sorry, just being blunt. Every expense is covered. They make EUR 100 million. We have a profit of EUR 20. Put it that way.
Okay. The Aemcolo, the diarrhea medicine, is going to be EUR 150, about, you said?
Yeah.
The price is not set, let me say that.
Yeah.
Around EUR 150.
What makes you so confident that Americans would pay that when a lot of medicines they can buy for $5, $10?
Sorry, which medicine?
Which one?
Well, no, I mean the over-the-counter, of course, and this one is a prescription.
Yeah.
This is not over-the-counter.
I know.
The over-the-counter.
I know
buy to stop the diarrhea. You cannot buy the treatment.
Yes.
If you would like to compare in terms of treatment our drug, you have to compare with the XIFAXAN.
Xifaxan.
The price of XIFAXAN is higher than our price.
To be-
You cannot compare with the Imodium.
Exactly.
Imodium is to stop the diarrhea. Sorry.
No.
Stop the diarrhea.
I was-
This is something that we treat. This is the very strong and big difference. Why is a revolutionary concept? Only because we are going to present to the travelers this opportunity because it make difficult. I have a question for you. Do you go in a gastroenterologist or a general practitioner before a trip, normally? You visit or you go.
No, of course not. It just seems to be a little bit high as an insurance to pay EUR 150.
Yeah.
You know.
As an insurance, we have to take into consideration that, as Sean is explaining very well, there is in the left part, the diarrhea, in the other part, the travelers. As an insurance, we have to ensure that a trip that is an average of 3,500 or 4,000 is a very, let me say, cheap that you spend EUR 150 just to ensure that you spend your time and you already pay not in the toilet, by the ocean.
Yeah.
It's better to close.
No. Let me also add one thing, which is important. If you start from the assumption that, say, Imodium is equal to our Aemcolo, this is just so wrong as an initial assumption that the discussion is completely out of focus. You cannot compare that with an antibiotic.
This is a revolution in the presentation only because We are going to present something that is difficult to do in the normal chain. If you have the reps, with the reps, you can go only to the doctors. The doctors, there are limited numbers of travelers that go to the doctors before a trip. This is the reason why the consideration of take the analyst, they believe that the travel area is a poor market. Is not a poor market. Is a market that is difficult to touch. Is difficult to reach with the normal chain, with the reps. We do believe that thanks to telemedicine and something that only the U.S. we can do, because you understand that only the U.S. who can promote directly to the travelers a prescription drug. This is important.
Thanks. One last.
It's the last.
The last.
The last.
The last. Absolutely last. There's now companies who developed tests for colon cancer, apparently. Could this be or do you regard this as a danger to the colonoscopies, that the number could diminish because-
Let me say that this is story in the U.S. The numbers of colonoscopy should became larger, and larger. More diagnosis you have, and more procedure you do. Because you have to take in consideration that just in the U.S., there are more than 15 million procedures. There is a lack of detection that the estimation, in my opinion, is not a right estimation. Is more than 20%. There is a lack of detection. Using the, I hope our, but using the artificial intelligence, you must have a dramatical reduction in the detection rate. Because detection rate, if you take our trial, for example. Our trial was 47% of ADR. ADR, normally in the multicenter study, they reach less than 20%, 20, 25%. Means that we have a lack of detection that you can estimate more than 25%-30%. Is a huge market.
More diagnosis will be, more procedures.
Let me also add one thing in this respect. First of all, that is a colon cancer test. The whole purpose of colonoscopy is to avoid colon cancer. I don't know if it's a relief to discover that you have colon cancer without having done a colonoscopy. The relief is to try to avoid colon cancer by doing a good colonoscopy so that you take away the adenomas before they turn into something bad. You see, the purpose is completely different. This is so true, that if you go through the papers of the company that you have in mind by mentioning this, they really don't claim that they will be able to substitute colonoscopy. They're claiming something different. They want to anticipate the screening and say, "I would like to screen also the population between 40 years old-
40, 50
50 years old by having them do this test rather than the colonoscopy, which is okay.
You can take-
Which is okay
U.S. for example. Sorry. If you take U.S. as example, you have the answer.
Colonoscopies overall, and every KOL will tell you, are expected to increase significantly over time.
Thanks a lot.
Thank you. I think we have Christian there, who has questions.
No. Yeah.
No, I called him before.
Sorry.
Sorry. Christian Sohl with Stifel. 3 questions, please. Just firstly on the device, just trying to understand the positioning of it, the relative benefits. You talk about the 47% detection rate with a device, but obviously from your trial, you had a 47% with a high-density white light, and you had 56% with methylene blue. Just trying to understand the positioning of the device versus existing techniques and the potential for using other dyes, doesn't have to be methylene blue. As I understand, presumably the videos were done in the trials. Were you using with the dye or without the dye? I wasn't clear on that. Secondly, just on Medtronic. Do you have any further you can say in terms of some of the economics around the deal or the commitments from Medtronic, in terms of the commercialization?
Were there any monies paid in recompense for research done in the past, in terms of what would you see as classical upfront type payments?
Let me answer this one first, because I have just been told by Martin that after your question, unfortunately, there will be no further time for questions.
There is another more question.
Okay, another more question. Okay.
Okay. Finally,
Answer to this question is the following. They're the biggest player in the world. Of course, there's a lot that's been agreed in terms of how this is going to be commercialized. We're not allowed to disclose, as you may understand, a lot of features of our agreement. It's just important, when you're asking about down payments, it's important for you to know that we deliberately negotiated not to receive a down payment in exchange of a very large, I would say, and unusual for Medtronic's usual or ordinary business, participation share in the revenues. This was deliberate decision from us. In respect of the ADR, the ADR that you're mentioning is not the ADR of the machine. What Nhan was mentioning is simply saying that by having the machine run on the same videos that had a 47% ADR, the machine confirms that it has the 47% ADR.
If you probably would have run the machine with a detection rate of 60%, the machine would have confirmed the 60%. What you don't know, and we will show later, is what's going to happen when you do this on a brand-new trial, which is probably the trial that we will do with the FDA.
Finally on remimazolam and remimazolam, what's the plans there around commercialization? Obviously, if you reduce Aries, presumably there are commitments there under the PAION agreement.
Oh, no. Absolutely. Commitment remains unchanged. Commitment is the same. I made very clear the point that what we have done is that we have laid off the sales force, meaning the reps, because they're not necessary for Aemcolo. We have kept the managerial infrastructure so we can build up another sales force just for remimazolam as soon as that will be needed. Time to hire a sales force in the U.S. is normally around two months.
Okay. Thank you.
Thank you. You have another question?
Yeah.
Oh, Pierre.
This micro works? Can you hear me? Okay. First, this is not a question. This is to thank you very much for this evening reception. I think we have very good news today. Also, some good questions, I agree, but very good news. My question is, what cruising speed of income could we expect in 2019 or 2020? In fact, an idea of a break-even point with existing situation. If you can.
It's a good question.
I think so. Mauro, you know why? Because I'm 85. I'm expecting to.
I agree.
I'm with you since 15 years.
I fully agree with you. I fully agree.
I think the answer should be, with all the fingers crossed, relatively straightforward. I think you know us very well. We're very cautious, we're not changing the guidance in any way or form. Our 2019 guidance is projecting a loss, excluding Cassiopea, we're not taking into account the proportion of loss attributable to our share in Cassiopea. We're projecting a loss of around EUR 12 million, but seven of those 12 are actually just accounting gimmicks that come from the stock option plan. The real loss in 2019 that we're foreseeing is EUR 5 million, which means that we can say that we can safely expect to return profitable in 2020. I hope this is.
Even in 2019.
Maybe even, yeah.
Thank you. That makes me very optimistic.
Okay. Thank you.
Okay.
No further questions? Thank you so much.
Thank you.