Thank you all for joining the Galapagos team for the 10th annual R&D update event at Galapagos. This is Elizabeth Goodwin speaking. I'm Vice President , Investor Relations. I'm joined here in New York by Sofie Van Gijsel , Bart Filius , Walid Abi-Saab , Piet Wigerinck , and about 100 investors and bankers. This year's R&D update marks an important inflection point for the company, as we stand at the cusp of our commercial phase with filgotinib while embarking on an exciting new R&D collaboration with Gilead. But before we begin, I do need to take care of a few logistics. You can find the webcast player via a link on our homepage. For those who'd like to join by telephone, please find the dial-in numbers and code on our homepage.
A replay of this presentation will be available on our website later today. We'll provide a reviewed transcript on our site in the course of next week. I need to start by reminding you that we'll be making forward-looking statements today. Actual results may differ from these statements. We refer to the full description of the risks of an investment in Galapagos in our most recently filed Form 20-F. Today, we're going to provide a snapshot of where we stand and where we're headed, zooming in on a few opportunities we'd like to highlight. Piet Wigerinck will speak on our delivery and R&D, update you on Toledo, and share his vision for future-proofing our productive research engine. Walid will cover filgotinib.
He will then be joined by Dr. Toby Maher, who will provide a clinician's perspective on IPF today, and then Walid will finish up with an update on the 1690 program. Bart will then speak on organizational growth at Galapagos and our future outlook. We estimate that this presentation will take about 90 minutes, leaving us time for Q&A before we wrap at approximately 9:45 A.M. till 10:00 A.M. At this point, I'd like to invite Dr. Piet Wigerinck , our Chief Scientific Officer, to kick off. Go ahead, Piet.
Thank you, Elizabeth. Good morning over here in New York. Good afternoon for those in Europe listening in on this call. Let me start with showing a bit what we've delivered in terms of R&D over the past 12 months. For those who are longer with us and follow us for a number of years, you know every year, we show these four key moments in a pipeline, which we believe if we keep on delivering on those, are important for our long-term growth and success. First of all, key for us is that we keep on looking and finding novel targets. Last year, we selected targets in the inflammation area, the metabolic area, fibrosis area, a new disease we added is osteoarthritis. Last year as well, I'm making immediate jump of a couple of years, we've delivered five PCCs to pre-clinical candidates.
In fact, that's what we end up at the end of the drug discovery phase. Five is in fact a new record. , so you can all be sure our teams have worked day and night to push this company forward. 4059 is a metabolic PCC. I'll show a couple of slides. 4124 is a novel molecule, novel mechanism of action in the fibrosis area. It's a chemically synthesized compound. The scale-up to the first batches will take a bit longer, but we'll move into the clinic after next year. 4259 is a backup in our inflammation pipeline. 4399 as well, I want to spend a couple of seconds later, is the third compound in the Toledo franchise we selected to move into preclinical development, has a unique profile. I'll touch upon that during my talk.
4471 as well is a backup of one of the compounds in the pipeline. In all five PCCs, three novel mechanisms of action. We really keep on delivering sufficient ammunition to grow the pipeline. Later in the pipeline, important for us is that we keep on doing novel proof of concepts. Out of these PCCs, a number will reach phase II, and the plan is for each of the compounds that reach phase II, we set up two proof of concepts. Last year, we set up for 1205, the PINTA in IPF , 1690 in Scleroderma , the NOVESA study . Finally, we believe long-term success, we need to keep starting one phase III every other year. If we can keep on that pace, we'll be set up for long-term growth. So, previous year, we started 1690.
This year, partner Gilead starts the PENGUIN phase III with filgotinib. Coming years, novel compounds will get to that stage. All in all, if you look to how much novel targets to PCCs to PoCs, we really maintain our pace, and we really set up for long-term growth and success. I also always show, in fact in discovery, the discovery area only, how much people work on here, just to give you an idea, an impression on how important diseases are. The inflammation area with the Toledo project is by far the most important. 40% of the people in discovery look for a new Toledo every day again. In fibrosis, about 30% of people work there on complete novel mechanisms of actions, pushing forward for either lung fibrosis, either liver fibrosis. We have the smaller areas. We call this inflammation, fibrosis are the strategic areas.
We typically have as well two tactic areas. Currently, we're switching between diseases. HBV is almost done, so you won't see it coming back next year. The new areas are OA and PCKD. PCKD is a polycystic kidney disease. The metabolic area is an effort we started a couple of years ago. It is currently at its height, will go down in terms of FTEs, but will keep on delivering a number of pre-clinical candidates planned over the coming years. These are our disease areas we focus on. With the expansion of the organization, we'll probably add one or two areas to that will come over time and is not a topic for today. All in all, we keep on being focused heavily on our strategic areas. Portfolio R&D. Well, in discovery we have around 30 projects.
When I talk to my friends in academic area, they say, "You're running a very hard model because you're stopping each year six projects." That's correct. We stop six projects every year. That as well gives us the room to start six to seven novel. We've been increasing the team slowly over the past years. The portfolio has grown a bit coming years as well as we go to the platform 2.0, this organization will substantially grow, will substantially deliver more over the coming years. Let me start now with a view on a completely novel activity, that is the metabolic area. GLPG4059 is a small molecule. It's being orally dosed, and it hits a complete novel mechanism of action, which is more focused around how the body handles lipids. It has nothing to do with SGLT2s, nothing with PD4s or whatever.
It's completely something coming out of the lipid area. My scientist really came to me and said, "Piet, this is really a target for type 2 diabetes. It has every promise we need to make it successful." We believe we are the only company working currently on this target. I'm not going to disclose this. We've been working for years first in rodents, and our rodent models are, in fact, completely normal mice we use. We put them for 12 weeks on what we call a Western diet, which is high fat, high sugar intake. After six weeks, we start to dose the mice with the drugs for six weeks. Here you see the outcome at the end of the six weeks. At the end of the 12 weeks of the experiment and six weeks of dosing.
What you can see is that the effect on the lipids, we always see a very clear drop of lipids circulating in the plasma. That's what we observed. The compound is given the dark green bars. We've included as a reference, just to give you an idea, is this marginal activity or is this decent activity, metformin. The gray are the healthy mice which keep on the normal diet. The orange bars are the ones that's been fed as well for 12 weeks. What we as well picked up quite early is a sustained decrease of body weight. So really, those mice lose a lot of fat and they lose body weight because they have much less fat in their body, similar to metformin here as well.
As well, finally, those mice, which is mice only, I agree with you, they handle much better all of the sugar content they are getting. Their fasting plasma glucose, that's what we measure in mice, is much lower than in disease state. Really, by blocking this novel mechanism of action, we see a number of parameters which we believe are important type 2 diabetes moving into the right direction. Having been working for three years almost on mice, I said, "Guys, it's time we confirm this as well in monkeys." That's what we recently did. Now we are looking here to diabetic monkeys. These are older monkeys, and they have all of the symptoms of type 2 diabetes. There are no healthy controls in this experiment. Which we've added in yellow a box where we combine our drug 4059 with metformin.
Ideas, if we move in type 2 diabetes, all patients will be on metformin, and we want to illustrate that we don't block that activity. It's not the idea immediately that with a single dose you see an increase in activity. It's just showing the principle when you combine them, patients will do well. Again, on the left, the lipids there, a nice drop of lipids compared to the disease. In the middle, the body weight change again as well in monkey, we see a nice drop. The combo seems to do a bit better in that indeed than metformin. Here we can measure HbA1c, so the glucose bound to hemoglobin. As well there we see a nice effect. That's one of the novel and the first projects in our metabolic program, which all in all is limited.
That has reached a stage where we currently are doing toxic studies with it. Hope to move it into phase I next year and then quickly move to type 2 diabetes patients, both as a monotherapy and on top of metformin. Just to give you a glimpse that we do more than just in inflammation and fibrosis only. Most of you, of course, are waiting for the Toledo update. I can understand that. It's the biggest program in discovery. It's the biggest program in early development. The whole team keeps on being fired up every day. In discovery, I must say, we're learning, getting surprises every day. In development, we're moving nicely forward and getting close to the patients. Why are we so fired up on this mechanism action? Well, let me try to explain you once more.
On the left, you see a normal, healthy people like most of us in the room here. We have an immune system which is ready to cope with infections, but which is kept under control by the purple dots which are the anti-inflammatory cytokines. If, unfortunately, you're suffering from an autoimmune disease, in fact, what happens is that your pro-inflammatory cytokines are in a clear excess, and you don't have sufficient of what you call here the immunocytokines. What's happening now with most of current therapies, what we do is well, we restore the balance. As there is no excess anymore of pro-inflammatory cytokines, they don't attack the body. You don't get ulcers anymore. You don't get joints which are attacked.
You put it nicely into balance, so the disease stops. Unfortunately, we all pay a price at that moment because for the next infections, these people don't have a fully powered immune system. That's what in effect we observe with Toledo, and that's why we're so fired up and so driven to bring this drug to patients and to the market. In effect, we again restore the balance. We see that, in effect, we have an intact immune system. These patients or patients in the future, when taking the Toledo compounds, they should be much more ready to cope with infections we all get every year. That's what tells us that if we can bring this to patients, we should deliver a complete new wave of anti-inflammatory drugs here with Toledo. There's the belief. Do we have some data to support it?
Let me show here. So with 3312, our first compound in the clinic, moving to IBD patients, we really went every layer we could go and ask our services not present. Of course, it is systemic activity, it's local activity. We really went down, measured the compounds in every level, but also measured the cytokines in the colon. It's not plasma, in the colon. You see exactly what I showed you on the previous slide, is that in those disease models you see an increase of the anti TNF— of TNF levels. With Toledo, you push that back. Unique here is that indeed, the anti-inflammatory cytokines, like IL-10 in diseases, you drop. The animals are not well-prepared. There, it's out of balance, Toledo pushes that up nicely.
According to us, it is the only approach there in the field that has this dual mechanism of action and that will restore the immunity in a way that patients won't suffer from their autoimmune disorder and will be better prepared if there's an infection upcoming. That's why we're so fired up. That's why we maintain the large team. That's why we maintain bringing novel PCCs forward. We have two in the clinic currently. We have 3312 moving to IBD patients. We have 3970. We started phase I this year, moving to multiple ascending dosing. This compound, compared to 3312, shows activity at almost the same dose level across all the models. This is a compound we will develop broadly across indications. These are a couple of examples. We have much more data, but on the joint models.
For 3312, we have fantastic activity in IBD, but we need to dose much higher in the joint models. For 3970, it is almost the same dose we are using there. You can see on the left in the CIA model for RA, a nice drop of disease activity. On the right, an IL-23 for the arthritis model, also a nice drop of disease activity. This compound really works in skin, in joints, in the GI tract, across all of the models, and I will show you that later again. We have different compounds there, and we keep on improving upon all of their properties. The family has three related targets. The disclosure of the target, I said, is not for today, so you can keep on guessing and doing whatever you like. 3312 is hitting each of these three targets.
We call it a pantol compounds. 3970 is only hitting TOL-2 and TOL-3. 4399 is a TOL-3 selective. Shows only the drop of TNF. Does not show the IL-10, it's a bit of a strange in the family. You're going to see them push this forward into proof of concept to see how well only this part of the activity as well is working. If it's a fantastic drug, we can still decide. This 4399 does not have the full promise, I want to stress that, of what a 3970 or a 3312 has. As you know, we test these compounds across multiple indications in the autoimmune space, we go beyond the classic borders of autoimmunity. The compounds don't work everywhere. None of the compounds work, for example, in OA. That's clear. Very clear.
3312 and 3970 has very similar profile with the difference that 3970, as it's going better into all the tissues, also shows some good activity in osteoporosis models. Fibrosis has been a surprise for us. We're diving deeper into that and might take the compounds into that area as well later if we fully understand what's happening there. TOL-3, as I said to you, 4399, the TOL-3 selective compound, has different profile. We don't see activity in IBD, so that IL-10 is really needed for that activity. We don't see activity in skin models because, again, that part of the activity is for some of the diseases really essential. In the joint models, 4399 is as good as any other compounds we've ever seen. We keep on pushing further. We're making TOL-2 selectives. We're mixing TOL-2, TOL-3. We'll always get surprises.
We keep on bringing novel chemistries, novel compounds forward, and we'll keep on doing that next year. Next year, we'll have patient data, and I'll show you what studies we plan. For 3312, we start a UC study. If that's going well, we develop a compound as well for Crohn's later . 3970, we'll explore much broader. We'll start three waves of studies. We first start couple of short-term POCs to validate what we see in animals we can translate into humans, will be the classical short-term POCs in inflammatory disorders. Middle of the year, we plan to start dose ranging. We really want to pick the right dose early on in the program as well, and we might start some longer-term POC studies as well there. Finally, those other indications which are beyond autoimmune probably will start around a year and next year.
They are shifted back also. We really first want to understand fully what is this compound doing across the autoimmune spectrum and move it forward quickly there. Not forget that we also see activity in the fibrosis models and in the OP models. Those indications are planned. That's so far my update for the Toledo today. Since we have that huge deal with Gilead, unfortunately, the question I get everywhere is not how good is your science, what are you going to do with the money? Which is in fact a quite boring question for me. What are you going to do with the money? Just want to find novel drugs, is the answer. We've been thinking for a long term, how can we do things better? Because working on novel mechanisms of actions, we had a limited pool of genes that we're targeting.
How and what's the smart way to expand here? I want to share with you our plans there as well. Our current approach in drug discovery has been for 20 years the same. We find novel targets, we drug them, and when we have a safe drug, we put in the clinic. We do a proof of concept, and when the proof of concept is fantastic, well, it can take us further into phase III and those ranges, and we bring to the market, and we start to sell. It was a very simple three-step approach. One of the limitations we saw is over past years is that finding novel targets in that selected pool of 6,000 druggable genes was becoming harder and harder. At the beginning, we had 15 and then 10, phase III.
We start to say, "Well, this pool probably it's a bit too small." First step we're going to do is really enlarge the pool and not going to the druggable only, but to the protein coding genome. We'll expand our pool from which we're going to start fishing. There's one risk if you start to expand the pool. The risk is that at the end of the screening, you're looking to a galaxy of all targets are lighting open. You have no clue how am I going to start here. What we need to do to keep science on track there is to really as well develop the pathways. The pathways tell us, in fact, within a disease how the different or some of those novel targets might be connected to science we know might be interlinked as well.
On the left you see here if you just work on novel targets and sometimes it's a scary picture, I can share that with you. For some of those targets we discover we have no clue how this is going to work. Even then, sometimes we start, but these are really the very difficult and the slow-moving programs. If you have an idea on which pathway they're working, drug discovery efforts become really much more efficient, and you have a goal in mean and a way to move forward. You really want to map this much better out rather than wait for others to bring us a map. You really want to approach is that you have the complete disease network.
You want to understand what's happening, the patient, what are the symptoms, the signs, what are the biomarkers, how is all of this playing, how is all of this traffic coming together in certain nodes so that you know if I hit it there, I'm going to see that. If I hit it somewhere else, it's going to be the impact. We're going to much more focus on novel targets we can link to pathways and build the disease networks around it so that we can really select the better pathways out of diseases. Those pathways, that's something I invented to give a short talk here. In fact, pathways is what we've learned over the past years how it works in patients. If you look here, if you would take an old school book on autoimmune disorders, they would order them by tissue.
You would have the disease of the joint together. You have had the disease of the skin together. You would have the diseases of the GI together. The vascular is a group on its own. After developing multiple drugs, in fact, we've learned that in fact you better group them by pathway. Some of these diseases are sensitive to IL-23, some to IL-17. There is a difference between IL-6 and IL-1. What we plan to do is what we've learned over the past 15 years to really get that info much earlier out of the patients and out of the cells. We're really going to add to the whole system a level of patient data. Recent years, the technologies have become available that allow you to look three levels lower than what we did until now. Let me give you an example here.
These are how we today look into the joints of our patients. We've always worked with tissues out of our patients, where we took the tissue as a whole and looked to the mixtures. Today with single cell sequencing, you can degrade the tissue up to a single cell level. You're going to sequence a couple of 1,000 cells. Now you can cluster those cells according to their gene expression into functional types. You can separate out the monocytes, the T- cells, the B- cells, the fibroblasts, whatever. You can measure the amount. That's the first. That's an easy level. You can go a little deeper. If you now look to what JAK is in all of these cells available, we could have saved ourselves 10 years of debate between JAK1, JAK2, and JAK3. There's only one JAK which is present in all of those cells.
If you really want to block in a joint, IL-6 signaling, the choice is made in a minute here. By looking into those cells, how they're active and how the different cell types work, you come to the right choices much more quicker than we ever did today. Of interest is a bit the blue-gray clustering there where people, in fact, never talk about. When we talk about our drugs in autoimmunity, we talk about T- cells and B- cells, and that's how difficult it is. We never talk about the fibroblasts. You have different types of fibroblasts. The way it's really becomes informative, if you can now cluster these or you can bring them back to how a joint really look like. Here, four colors for the four different types of fibroblasts. You can see it.
You have a green, a red, an orange, and a blue. One type 1 of fibroblast you see the lining. The second layer is the blue one. You have the red ones which are in the blood vessels, and you have the green ones which are just around the blood vessels. With all of this type of information and now looking what's going wrong in patients, what's going wrong in patients that don't respond, will be much better fit to select the promising targets and developing better drugs for even already where we stand today. So that's the first level on how we're going to upgrade our targets of the platform.
Next to that, we are extremely proud on our small molecule platform, but we've always also had couple of targets where we block the enzyme and nothing happened in the disease, where we could not block the enzyme, where it was a target, say, well, it is doing everything right, but we don't find a way to modulate. We're going to as well expand on the type of drugs we want to develop. Let me explain it quite simple. Industry always worked on the right of this cartoon. We always made compounds that activate or block targets. These are the small molecules that has been the origin of this industry, has been the focus. They've supplemented with peptides and antibodies, cell therapies, but we've always worked on the right-hand side. In theory, for every target with drug today, you could go to the genome, knock it out.
Could say, "Okay, let's keep the genome intact." We go and work at the RNA level doing an siRNA or an antisense, or we work on the protein, but we don't want to influence the function of the protein. We want to influence the concentration of the protein. If you just make that the protein disappears as well, you, in theory, could have a good type of novel drugs. What have we selected out of these modalities? We've highlighted them in orange. We'll keep on working on small molecules, so don't panic and run out the room that they're going to change everything. We're going to build further on our expertise.
We're going to add on what we've been working on in the lab for a number of years, is to, as soon as we have binders to proteins, direct those binders to the enzymes that degrade, or the cellular components that degrade proteins themselves. That's what they call the PROTACs. Also can do the inverse trick, what we learned in the CF area. You can add compounds that influence the conformation of a protein, so the protein is much more prone to the enzymes. The other hand, if you see what our platform does, our platform, in fact, is a knockout platform or knockdown platform. We're knocking down a target. So, we as well are going to invest into siRNA type of drugs where we're going to work at that level to decrease the amount of protein.
Quite honestly, what we've seen in the HBV field tells you this technology is ready for more diseases than HBV and a number of muscle diseases only. In overview, we'll keep on doing small molecule discovery. Don't worry. For those targets where an inhibitor and activator doesn't work, we're going to use other tricks to degrade the amount of protein. It's going to be in the first wave, the PROTACs, late the small molecule, because it takes time to build up a platform. Finally, in order to also much more efficient drug discovery, we're going to bring in siRNA type of work to really, from our knockdown platform, immediately map the pathways, immediately select the models, that we much faster can select out the promising targets and the drugs. Eventually, if we're good enough, even bring in siRNA to the market or to the clinic ourselves.
That's the expansion we are planning. We are actively looking and searching. We're going to build, collaborate, acquire a number of what we need to do to indeed get this ready within a couple of years. Looking at the highest level. So, currently, we work on about 6,000 genes. Yearly, get more or less six small molecule targets out of that, and that translate then into three PCCs on a yearly basis. That's currently, if you look on how we plan the organization. Over the coming years, going to expand the pool from 6,000 to more than 20,000. We'll have more hits, we'll need the pathways to guide us, to help us selecting the targets. With siRNAs and all of that, we can take a number of targets immediately to the right track here. We'll as well have more starting points for the small molecules.
So, ideas will be able of starting more small molecule programs and deliver more PCCs, either as the classic small molecules, either as PROTAC that degrade the proteins, either as siRNAs that inhibit the formation of the proteins. That's so far for my talk. I now invite Walid show us on filgotinib, our latest use.
Okay. Good morning, everybody. Good afternoon for some of you who are on the phone joining from other parts of the world. Thank you, Piet, for walking us through this early part. Let me tell you a little bit about filgotinib, and where we are heading. So, we've been talking about filgotinib. It's really been a pipeline and a drug. We're very happy with the way this program has been progressing very nicely.
And it is.. It's essentially profile, and it's risk benefit profile has been becoming more and more crystallized with every new data that we get. As you know, earlier this summer, we submitted the dossier in Europe. More recently, we submitted the dossier for approval in Japan, and we're working relentlessly on finishing up the dossier and submitting it to the U.S. before the end of the year. Our phase III program in IBD is progressing very nicely.
These are both studies in UC and CD, Crohn's disease and ulcerative colitis . Ulcerative colitis program, as we've been communicating before, finished recruitment and now we're going through the in-life phase of the trial, and we expect to have top-line results by the second quarter of this coming year. We have also going beyond, in other rheumatology indication beyond RA, in particular psoriatic arthritis and ankylosing spondylitis. Our psoriatic arthritis program, I'll talk about it a bit later today, is actually active now, and our ankylosing spondylitis program is getting ready for a start early next year. When you look at the RA space, you realize how large of a market inflammation is expected to be by 2027. We're talking about EUR 65 billion.
If you look at the indications that we're in beyond RA, particularly IBD and ankylosing spondylitis, psoriatic arthritis, those would represent more than 60% of the market. In those spaces, particularly in the IBD space, which is the lion's share of that additional space, we will be in a very competitive position or being either first or second to market. We believe this will put us in a very good shape, considering our efficacy profile that continues to manifest itself, and also the very favorable safety profile that we have, giving us the potential to be best in. In psoriatic arthritis, we're getting ready to move on into the phase III program. This is a disease with a high unmet medical need. This represents about a third of the patients of psoriasis. They have joint involvement as well.
And these tend to be more difficult to treat than RA. Usually, the response rates are a little bit lower than RA. This is the EQUATOR study that we shared with you last year. We were quite impressed by the level of efficacy that we've seen in this trial. This was a trial of about 65 patients per arm, so 130 total, given filgotinib 200 or placebo in a one-to-one ratio, treated for 16 weeks. And you can see the ACR20 response here are in the upper 80%. ACR50, more than 50%, and even ACR70 in the short duration in these more difficult to treat type of population is getting close to 30%. These data look very promising, and based on that, we continue the development of this compound. Just recently at ACR, we shared the data from the long-term extension of this trial.
At the end of those 16 weeks, those who are on placebo will get given, in an open label fashion, filgotinib 200 . Those who are on filgotinib 200 will continue their treatment. Here you can see how the effects have been sustained, both on ACR20, ACR50, and ACR80. The numbers continue to look very good and are maintained throughout the year. Also, the safety story continues to be as impressive and consistent with what we've seen before. On the left-hand side, these are the safety that were seen in the first 16 weeks of treatment with filgotinib and placebo, so you can compare. And here, we selected the adverse event of interest, like serious infection, opportunistic infection, zoster, DVTs, and so on and so forth.
What you can see on the right-hand side, which comprises all the data up to week 52, that there's been no significantly additional events that we've seen. No DVTs or PEs, no additional death. There was one additional MACE, maybe a couple of serious infections. What you see on the right-hand graph for the totality of the safety is we express it as event per 100 patient years, because that also would be helpful to compare to the rest of the data that we generate from RA program. As you can see, those rates continue to be looking very favorable and very consistent with our RA program.
So one of the key things for me for filgotinib is it really has been performing in a very consistent manner, regardless of which indication you put it in, which makes me feel very good about the likelihood of success in the future when it becomes available to patients. Let's talk a little bit about the phase III program that we're moving forward with in ankylosing spondylitis . It's called PENGUIN. It's going to be similar to our RA program at high level in that we will explore both doses of filgotinib, 100 and 200. PENGUIN 1, high level, it looks like FINCH 1, if you want to. This is in methotrexate-IR. It's a 24-week double-blind placebo control and active control, so adalimumab is also the active control. The primary endpoint will be at week 12. There will be two doses of filgotinib.
Then at the end of those 24 weeks, the patients will be then either continue on their original dose if they were randomized to filgotinib 100 or 200. If they were on placebo or adalimumab, they will be re-randomized to filgotinib 100 to 200. They will continue equivalent to a FINCH 4 with a long-term extension where their treatment assignment to dose will be blinded, but everybody will be on filgotinib. PENGUIN 2 is the biological IR population. It will be two doses versus placebo. The double-blind portion of the study will be 16 weeks. Primary endpoint will be at week 12. Primary endpoint, by the way, for both studies will be ACR20. Again, at the end of the 16 weeks, the patients who are on placebo will be re-randomized to filgotinib 100, 200.
Those who were on 100, 200 will continue in a blinded manner in terms of dose assignment. We've been talking from the beginning that we want to go after JAK1. That's been something that is driven from the science, and you've heard Piet talk about it earlier today as well, about how we go about looking at these things. From the get-go, our hypothesis was you need to block JAK1. That's the only thing you need to bring inflammation under control. And sparing JAK2 and JAK3 pathways will allow these pathways to continue to be active and functional as they should be in the body if you don't need to block them. Otherwise, you're going to start earning off-target activities and increase in side effects. We designed filgotinib specifically with that in mind.
As you can see on the panel on the right, we've shown these data before in our whole blood assay, and those have been validated from some external work from McInnes and others that have been published, that our compound has been highly selective for JAK1 versus JAK2 in the left-hand side graph, and also highly selective JAK1 versus JAK3 in the right-hand side graph, which with about 25-fold in both cases. This is specifically designed so that you have enough headroom so that when you go in the clinic, you go as high as possible so that you can achieve maximum JAK1 inhibition in the majority of patients without hitting JAK2 or JAK3 and stay away from any liability. Actually, that's kind of what we see.
When you look at the totality of the data, I'm not going to recap this because we've been published, we've been talking about it for some time. We've seen that the JAK1 inhibition of filgotinib is sufficient to address inflammation. If you look at our efficacy across the board, you see that we work early on. We have deep and sustained efficacy that is maintained. Also we work across the board, whether you have early RA and you're naive to methotrexate, whether you are methotrexate incomplete responder, or even on the other end of the spectrum, biologic incomplete responders. As a matter of fact, we've also shown recently some subgroup analyses at ACR, where it doesn't matter whether you've been exposed to one, two, or three previous, or three or more of previous biologics and you have not responded, your response to filgotinib is the same.
Very robust, very sustained efficacy, and you see it very early. Importantly, this comes without additional liability of target activities. These are the data, summarize the safety of some key important elements that if you think of the JAK class in general, people raise questions. Well, we're not sure a little bit about the increased risks of serious infections, increased risk of herpes, or increased risk of thromboembolic events . Well, here they are. These are data from our FINCH program, more than 3,500 people, more than 2,000 exposed to filgotinib on the far right-hand column. You have the people on adalimumab in the middle, about 300 patients. Those on the left are the placebo and methotrexate active treatment from FINCH 1, FINCH 2, FINCH 3 lumped together for about 1,000 patients. Here you can see the risk of serious infections, herpes, DVTs, and death.
They're really similar across the board. There's no significant uptick in the case of filgotinib, they look very competitive when you look at what's been published out there, what's known out there from other JAK inhibitors. And here you look at the data from our DARWIN 3 study. This is a long-term extension of our DARWIN program. We've been reporting on it on an ongoing basis as we accrue more data. A few days ago, we showed these data at ACR, you can see up to week 156, we have more than 2,200 patient year exposure. Here I'm showing the data in event per 100 patient years. Again, you see these rates for serious infection, zoster, DVTs, PE, and death. The rates are quite low. I point your attention for DVTs and PEs. I'm sure you've spotted it as well.
The rate is at 0.1. This is very, very low if you've been looking at data from other JAKs out there as well. To conclude, we believe that filgotinib has been designed with that selectivity in mind, and we're very happy to see that clinically it continues to display JAK1 selectivity. It brings us strong efficacy across all the kinds of symptoms of RA, across a wide range of RA patients from the mildest to the most severe patients. It does that in a way that does not interfere with other JAK signaling, and you can see that clearly by the fact that we normalized certain laboratory parameters that are abnormal in inflammation. Specifically, I'm thinking about hemoglobin changes and platelet changes. In addition, it has a clear safety profile, which is, in our opinion, a result of this high selectivity.
You see that across the board and continues to be confirmed the more data we add. With that, I'm going to finish my talk on filgotinib and switch gear. Actually, we are very fortunate today to have with us Professor Toby Maher, who has been actually with the program-1690 longer than I have, since he's been involved in the design of the FLORA study with us from the beginning. He's been the lead PI on that study, and he's been also with us with ISABELA and the lead PI on this. I'll just say a couple of words about who he is, and then he'll tell you much more about it in a minute.
Professor Maher, he's a Professor of Interstitial Lung Disease at the National Heart and Lung Institute at Imperial College London. He's also Director of Respiratory Research at the Royal Brompton Hospital in London as well. We've been very fortunate to be working with him for the past several years and many more to go. Toby?
Walid. That was far too many words about me. I'm going to talk to you about idiopathic pulmonary fibrosis, which obviously has been a large focus for Galapagos over recent years. Just to tell you a little bit about myself in my own words. I work here at the Royal Brompton Hospital . It was built in 1844, which makes it quite old, I guess, by American standards. It was originally a TB sanatorium. It became a thoracic diseases hospital. The lady there, Dame Margaret Turner-Warwick, actually set up our lung fibrosis unit in the 1960s, a long time before anyone else became interested in fibrotic lung disease. As a consequence, my service currently looks after about 1,500 new patients with pulmonary fibrosis each year. We have about 5,000 patients under our care at any one time.
That's given me a great opportunity to run clinical trials, and we've recruited more than 500 patients into clinical trials over the last decade. We've got extensive background in running clinical studies. As Walid said, I got to know Galapagos, I think it was 2013 or 2014, so a fair while ago now. What is IPF? IPF is a progressive scarring disorder of the lung. It tends to affect older adults. In many ways, you can think of it as the sort of lung equivalent of Alzheimer's disease. It's the lung prematurely aging in advance of the rest of the individual. As the lung scars, it becomes less effective as an organ of gas exchange. Obviously, our lungs are working to get oxygen into our body, carbon dioxide out of it. As that scarring process progresses, people become breathless.
They ultimately slip into respiratory failure, ultimately they die as a consequence of their disease. It's a pretty nasty condition to have. Without treatment, the median survival is about two to three years from diagnosis. Five-year survival is around 20%. The graph here just compares the five-year survival of idiopathic pulmonary fibrosis to a variety of cancers. I think one thing to notice is that the five-year survival of many of these cancers is a lot better now than it was 20 years ago. The same cannot be said for IPF, where we've seen little change in outcome until very recently. Moreover, IPF has a prognosis that's very similar to adenocarcinoma of the lung. Whilst it's not a malignant disease, it has an outlook akin to malignancy. What's important is that it's becoming more common.
At the moment, FDA, the European Medicines Agency, consider IPF to be an orphan disease. Truth be told, it isn't. In the United Kingdom, one in every 100 people who dies as a consequence of IPF. Same is probably true in the U.S. Probably 100 of us in this room, so at least one of us is going to go from IPF. Probably not an orphan disease, but we won't tell the FDA that. At the moment, there are probably 40,000-50,000 new diagnoses of IPF in the U.S. each year. There are probably 250,000 or more people living with the condition as it stands. As I've told you, it's a disease of aging. Our average patient is a man in his mid to late 60s.
We suspect that men are more affected than women, probably because of past smoking habits and also because of exposure to dust in the industrial setting. That said, IPF doesn't really respect social class, and it's a disease that we see affecting a wide range of individuals. We've begun to understand a lot about the pathogenesis of the disease, which is obviously important when it comes to thinking about developing new treatments. We recognize that there's a genetic component. About 5%-10% of our patients will have a family member who's also suffered with pulmonary fibrosis. We're increasingly recognizing the genes that are responsible for making individuals susceptible to developing the disease. The second thing that's important is a lifetime of injury to the lung. Obviously we're breathing in five liters of air every minute. That air contains dust, contains other people's cigarette smoke.
It contains viral and bacterial particles. And all of those things are causing little bits of damage to our lungs day in, day out. It seems there is a threshold at which, once you increase the level of damage that you experience during a lifetime, you become more likely to develop IPF. The final piece of the jigsaw is getting older. I think those factors are important because we are seeing the disease increase in incidence. We have, in the last 20 years, seen a doubling in the number of new cases, and we haven't seen that plateau yet. And that's partly because we have an aging population. It's partly, I suspect, because we are seeing changing patterns of air pollution. We're seeing damage from microparticles, diesel fuel, which may well be triggering damage that leads to fibrosis.
I think the third important thing is we're getting better at treating all these other diseases like cardiovascular disease and malignancy, and as a consequence, our patients are living long enough to get IPF. Anyway, once the disease triggers, we see activation of multiple pathways involved in the normal wound healing response, and that leads to fibroproliferation and fibrosis. It's the same process that would happen if you scar the skin after injury or surgery, but it becomes uncontrolled and self-perpetuating in the lungs of patients with the disease. As I've alluded to, clinically, we see our patients become progressively breathless. At the start of disease, they're only breathless when they heavily exert themselves. By end of disease, they'll be oxygen-dependent. It's worth reiterating that the majority of patients who develop IPF die from IPF.
This is not something like prostate cancer, where 80% of the population get it, but only a small proportion die from it. Instead, 80% of patients who get IPF die from respiratory failure as a consequence of their disease. From a clinical perspective, we do see different patterns of disease behavior. We typically measure disease progression using forced vital capacity, which is a measure of lung volume. We get patients to blow out from a maximal inspiratory effort all the way out, and that gives you a measure of lung volume. We've used this technique to sort of measure patients' day-by-day disease behavior. The graph here represents one individual who's done his forced vital capacity every day for 18 months. You can see the gradual rate of progression in his disease. He'd lost about 10% of his lung function in 12 months.
This is another individual, much more rapidly progressive disease. He died 220 days after entering this study. This is the third pattern that we see. This patient had an acute deterioration, and actually, patients with pulmonary fibrosis are uniquely susceptible to lung injury. When they develop something like an infection, they get widespread inflammation and damage of the lungs, and o nce that happens, they've got a 50% chance of being dead within the next month. This patient actually started off with well-preserved lung function, and you can see after the deterioration, his lung function plateaued for a while. Nonetheless, these episodes affect about one in 20 of our patients each year, and are one of the leading causes of death that we see. We can use forced vital capacity to understand disease progression in the individual patient.
We've also used forced vital capacity to help develop better trials. The FDA are now very happy with using rate of change in forced vital capacity as their primary endpoint of choice for approval studies in IPF. I want to keep hammering home how bad this disease is. In case you haven't got the message, bad disease, none of us want it, but one of us probably will get it. This is just what happens to the patients I see in my clinic. If I see 100 new patients in a month, I can pretty much work out what will happen to them over the next three to five years. Unfortunately, people still present quite late with this disease, so even at diagnosis, about 15% of patients will already be oxygen requiring.
If I go a year down the line, during that first year, we have some of those patients with very rapidly progressive disease. About 20% of patients will be dead by the end of one year, and some of the remainder will have slipped into respiratory failure. After the first year, the death rate sort of settles down at about 15% a year, which means that by the end of year three, half the population are dead, and a proportion now are oxygen requiring. If we fast-forward to five years, somewhere around 20% of my patients will still be alive five years after that initial diagnosis, but only a small proportion of them will be off oxygen and actually leading any semblance of a normal life. We have seen the development of treatments. There are two FDA-approved therapies. There is pirfenidone.
This was the pivotal trial which showed that pirfenidone slows the rate of disease decline as measured by FVC, by about 50%. The other drug is nintedanib. Again, a similar magnitude of benefit in terms of slowing FVC decline. Those drugs were both approved in late 2014, so we've now got five or more years' experience in using them. We are beginning to see some improvements in survival for our patients. Both the European and Australian registry have been able to show that even when you normalize for baseline disease severity, there appears to be an improvement for patients treated with antifibrotic drugs. I'll highlight this graph here. This was some work we did with data available from open label trials of patients on pirfenidone. These patients had been on treatment for 10 years or more.
Comparing them to historic severity matched patients, we found that pirfenidone probably gives two years extra life expectancy to our patients. The third line on the graph is the normal life expectancy for the average 67-year-old in a Western population, 67 being the average age of the patients in the clinical trial. So, you can see that patients, even on anti-fibrotic drugs, still have a deficit in life expectancy of approximately 12-15 years. Although we've seen some advances, we've still got a long way to go to try and make life normal for our patients with this disease. I think the other thing that's been important, is that we've now seen the use of these anti-fibrotic drugs in other forms of lung fibrosis.
Whilst we focused on idiopathic pulmonary fibrosis as the worst of the fibrosing lung diseases, we actually, for every one of our IPF patients, see two other patients with different forms of fibrosis. It can arise in the context of connective tissue disease, so rheumatoid arthritis, systemic sclerosis. We also see a range of other conditions, things like asbestosis or chronic hypersensitivity pneumonitis. All of these cause scarring of the lungs, and the majority of them go on to cause death, sometime a little more slowly than with idiopathic pulmonary fibrosis. This was the data from the pivotal study done with nintedanib in patients with Scleroderma-associated ILD, and the FDA have now approved nintedanib for this indication, and they've given it breakthrough designation for chronic fibrosis of any form in the lung.
And so, the hope would be that if we can identify another drug that treats IPF, we will be able to demonstrate that that's effective in that even bigger population of patients who also have fibrosis. As Walid said, I was fortunate enough to be involved with the FLORA study, the phase II study of GLPG1690 in IPF patients. We presented the data. I didn't choose this picture, by the way. I wouldn't normally put pictures of myself in a presentation. It was done on my behalf. This was us presenting the data at the ATS meeting a year ago. Walid, I think, is going to talk to the results in a second. I'll just wrap up. These are pictures of my patients attending open days that we held. I still see lots of people dying very sadly of respiratory failure.
It's a nasty way to go. As I've told you, it's not truly an orphan disease. It's becoming increasingly common. We've shown with pirfenidone and nintedanib that fibrosis can be treated, and there is a pathway to approval. Those drugs have tolerability issues, and we've still got a long way to go to restore normal life expectancy to the patients I see in clinic. So, from my perspective, it's fantastic that Galapagos are working on this disease much.
Very good. Well, thank you, Toby. It's a very sobering talk. At the same time, it's also very motivating for those of us who are working on this disease. As you know, Galapagos really is putting IPF in its crosshairs, we have a number of approaches to try and tackle this disease. Let me tell you a little bit about our program with 1690. I think Toby touched on this a bit, the fact that the drugs that we have currently have significant limitations. Although they do reduce FVC decline by about 50%, the problem is also that they have some tolerability issues. In real-world settings, about a quarter of the patients do not take these medications. They discontinue about at a rate of about 25% per year, because they don't tolerate it, or they don't see effects from it.
Despite that, the market size in 2018 was more than $2 billion for these two drugs, pirfenidone and nintedanib. Maybe about a little bit of background. Just bear with me. I'm just going to walk you through a bit our story there. How does 1690 work? We need to take a step back and look at the autotaxin as a target. On the left-hand side of the graph, you see a cartoon, which is taken from a "New England Journal" paper by David Lederer , where he was reviewing the various mechanism actions of these compounds. You can see the pathway that we're talking about here highlighted. The autotaxin enzyme is widely expressed.
It is responsible for converting lysophosphatidylcholine to the bioactive lipid lysophosphatidic acid, which in turn then works through a number of different receptors of at least six G protein-coupled receptors, to produce its activity. It's known to essentially regulate diverse cellular processes such as proliferation, differentiation, and migration, and these have been involved and have been linked to a variety of diseases, particularly in inflammation and fibrosis. One of the things about 1690 is that it has a dual role in the way it blocks autotaxin. So, essentially it blocks the type IV enzyme, which is not only responsible for blocking the enzyme itself, but it also blocks the transport of LPA1 as foreign .
So, it has a dual mechanism action, which we expect that it will render it much more potent in controlling LPA levels. Based on that science, and there's a lot more which I'm skipping over that were done in Piet's labs, we embarked on the FLORA study where we studied, in a small proof of concept study of about 23 patients, the effects of 1690 at 600 mg once daily over a period of 12 weeks. This trial was randomized 3:1, drug versus placebo. We looked at a number of endpoints, including changes in LPA levels in the blood. In addition, we looked at FVC. The study was not powered to detect changes in FVC because of the size of it. It was mostly designed to look at safety and tolerability as well as pharmacodynamic effect.
We were very surprised by what we were able to see, which you can see here on the graph, what seems like stabilization of the lung functions in patients receiving drug. About at the end of the trial of 12 weeks, there was about 100 mil difference between drug versus placebo in this [office-based] spirometry. Actually, those data were corroborated by home-based spirometry, and you can see these data in The Lancet paper that was published, where also the difference over time was about 100 mils between the two. When you couple that with the clear effects that we've seen on imaging, we used functional respiratory imaging where we showed that the drug essentially stabilized the disease completely as opposed to the placebo patients who continued to decline, and a safety profile that looked very promising.
We were very excited to embark in further development of this compound. As we are moving and preparing for it, we had a very nice surprise in that BMS actually validated the autotaxin pathway in patients with IPF. This is a study from BMS. This is a compound, if you remember on the previous slide that I showed with the cartoon. This is a compound that blocks LPA1 receptor. This is a compound by BMS. It was put in a double-blind placebo-controlled trial, which was a reasonable size, about 50 per group, so 150 patients total, treated for about six months. You can see very nicely on the graph on the right-hand side a dose-dependent effect in reduction in FVC decline over this time, reaching statistical significance at the top dose.
Now, unfortunately, this drug had off-target activity that led to liver toxicity in humans and the study was stopped. But BMS has published that they were able to find another molecule earlier in development with the same mechanism of action that does not suffer from these toxicities in animals, and they are continuing now its development as far as I know. What does our ISABELA program look like? So, this program is made of two identical trials, each comprising 750 patients. They will be randomized in a one-to-one ratio to placebo or two doses of 1690, 200 or 600 mg once daily. The patients will be virtually all comers.
Essentially patients who are on standard of care are welcome, whether that includes anti-fibrotic therapy as in pirfenidone or nintedanib, or on neither of them, but they are on some supportive care or for whatever reason they're not on this medication, they're allowed to come in. We expect in the end, and that's what we target to have about a third of the patients on pirfenidone, about a third on nintedanib, and a third on neither of them, because that is how the situation is in the Western world, the U.S. and-- We're going on top of standard of care, we can afford to keep the patients on their randomized treatment even after the primary endpoint at week 52, until the last patient crosses the 52-week line, which means everybody else would have gone much longer than that.
If you think about one and a half to two years of life part of the study, so some patients would have been on this up to even three years. This will allow us actually to capture, in a randomized, placebo-controlled way, these events that are rare, that often do not happen in a very short trial. Things that are very important hard endpoints, such as death or hospitalization due to respiratory failure. Here you can see it also very clearly that this program is quite innovative. It's the largest that we have that has been done so far in IPF. It's the closest to real-world setting, which is very helpful for the clinicians later so that they know how the drug will perform in as close setting as what they will see in the clinic.
Also will generate not only data on the primary endpoint, which is FVC, which is the regulatory accepted endpoint, but also generate data on these important endpoint such as death and respiratory hospitalization. On top of that, we will have large safety data in 1,500 patients, not only for a year, but also for much longer periods of time. Where are we in the program? This is a very large program. It's a first for us at Galapagos. We're very proud of it. We're going to be in approximately 250 sites worldwide. Here you can see the distribution spanning from North America to Latin America to Europe, of course, even Africa and Southeast Asia, including Japan. Japan has been the recent addition, I should say, to-- to our, you know, to our sites after having discussed the plan and agreed to it with the PMDA.
We're very happy now to start in Japan. We'll be able to recruit the required number of patients so that in the end, we will do a global submission in Japan, U.S., and Europe around the same time. We don't have to do something specific for Japan. We are virtually finished activating more than 90% of the sites and the study is progressing very nicely. This gives you a little bit of a timeline that we have. We're very happy to say that we are a third recruited so far, so we have 500 patients on the trial out of the 1,500. This is ahead of plan that we have put together very carefully with our partner CRO.
And I think the feedback that we get from the sites and from the various patient organizations, and I think maybe afterwards you can ask Toby some questions himself as well, has been very favorable. We've also talked about the need to do futility analysis because, again, we jumped from a small study to a much larger program. We want to make sure that if the results in FLORA were completely a fluke and the drug doesn't do anything, that we stop the program before we go all the way out. In order to do that, we did a robust analysis statistically to be able to see what are the operating characteristics of the program, such that we can identify what is the number of patients we would need in order to make the right decision.
What you don't want to do is stop the program when the drug still has efficacy and could be meaningful in the end, or let the program continue if you have nothing. In doing so, we reached the conclusion that we need about a third of the patient or about maybe 30% of the patients to clear week 52. With that totality of the data, we will have enough information to make that decision in a wise way. It's really a robust futility analysis that we plan to conduct. We have reached the target, we think, of the patient recruited now. Now we need to get them through the trial. We expect by this time next year should have enough of the information that we need. We need to bring the data in, analyze it, have it go through the independent data monitoring committee.
We expect that we'll be able to communicate on this in the first quarter of 2021 or early in that quarter as well. As I said, the recruitment is going very well. We're very excited. I can say with confidence that around this time next year, we should be done with recruitment. Then you can imagine it's going to take a year to get through the patients, to get through the treatments, and then the follow-up visits and getting the data in. I expect that we should be able to communicate top-line results in the early part of 2022. With that, I think I've covered all that I wanted to cover around IPF and filgotinib earlier. I'll turn it over to Bart to tell us a little bit about how we're going to be growing and going forward from here.
Thank you, Walid. Let me say a few words in conclusion on how we're going to build out our company towards a fully integrated biopharma company, and also take a quick second to reflect on the transaction that we signed earlier this year with our partner, Gilead. This slide is familiar to most of you, I would say. I think given the size as well as the complexity of this transaction, I think it's worthwhile to highlight a couple of aspects here. First of all, our transaction that we've signed with Gilead is lasting 10 years. As a result, it provides Galapagos a very important time period of independence and ability to invest in our own R&D platform with all the strengths that Piet and Walid have been showing earlier on this morning, and allowing to build that forward on a standalone basis.
It's also important from a financial point of view. We've received $4 billion of upfront for the transaction that we've signed in July, received this in August. I remind you that there's further opt-in fees and milestones connected to the various programs. There is a license built in already on 1690, our program in IPF, but there's an opt-in moment for 1972, our osteoarthritis program, and that probably is going to take place somewhere in the course of next year, that type decision. There's further opt-in options when programs achieve the end of phase II in our pipeline. Significantly, also in terms of cash. Also in equity investment, this number has gone up since a previous slide that you've seen because Gilead has had also the right to increase their stake to a level of 25% by the exercise of a specific warrant.
That warrant has been exercised meanwhile. Last week they've increased their stake to 25.1%. I think we've issued a press release on this as well. The total amounts received for the equity investment is now $1.5 billion. Finally, that's obviously a key component of the economics of our collaboration with Gilead, that we are receiving royalties on all our product that start at 20%, they go up to 24%. That's obviously a very meaningful percentage. In case you're wondering, is there future exposure economically to the U.S. at Galapagos? The answer is definitely yes. We receive royalties on all of Gilead's sales outside of Europe, and we retain 100% of the European economics. This is slightly different than the filgotinib transaction, where it's royalties and a profit share in Europe.
We retain all of Europe for Galapagos during the collaboration for all our programs. That's important because it allows us to make the next step also operationally and build the next leg to our company, which is also the commercial leg, and make sure that we become a commercial powerhouse. First in Europe. Then you never know down the line when we'll make the shift also to the U.S. First we're focusing clearly as part of this transaction on Europe. We do this with our first opportunity around filgotinib, where we have a joint co-commercialization agreement in place, and we have extended the operational rights as part of the Gilead collaboration to be the launching company of filgotinib in rheumatoid arthritis in three out of the five EU-- five countries.
Spain, France, and Italy will be launched in RA by Galapagos, whereas Gilead will launch in Germany and the U.K. in RA. We've swapped our territories for our subsequent launches. When we go to IBD, first in line will be UC. We will be launching in Germany and the U.K., and Gilead will launch in Spain, France, and Italy. Not on this chart, but the Benelux has always been part of the exclusive territory for Galapagos. We'll be launching all indications in Galapagos. In case you're wondering, why is this the choice that we've made? Obviously, in any type of co-commercialization agreements, you need to make sure that you organize something as efficiently as possible in the best interest of the molecule.
We've came to the conclusion that a split by indication is the most efficient and appropriate manner to organize ourselves in this co-commercialization. At the same time, it allows both companies also to book revenues in all of these territories. We will be the revenue booking entity for Spain, France, Italy, and the Benelux, whereas Germany and the U.K., for all indication sales, revenue will be booked by Gilead. It will also really allow us to build our infrastructure in a phased manner. The focus clearly now is on those first countries, and we have a little bit more time, even though not that much, a little bit more time to build out our own infrastructure also in Germany and the U.K.
As the RA lead company in those countries, we will be also responsible for the physical distribution, and we will also be the party who will negotiate and execute on access negotiations with governments. We are really in full launch mode with filgotinib as we speak. That's important because obviously, time is short until actual launch. We hope to have an approval in Europe in the second half of 2020. A little less than a year from now, and we will be launching very shortly thereafter in our countries. We anticipate that probably the Benelux countries or Holland will be one of the first, but France will follow very shortly thereafter, while Gilead will ensure that the launch in Germany, which is most likely going to be the first country in our launch, will be executed perfectly.
By doing so, we're establishing Galapagos in all of those countries. We are engaging with the key opinion leaders. We were already doing this for a while, obviously. We are bringing this forward. We're working on the access. We have all the access teams in place. We're building things like the physical supply chain and all the support functions as well. As I said, UC will give us a bit of extra time for Germany and the U.K., but not even that much. Earlier, you've seen that we expected data in UC in the first half of 2020. If you then roll forwards with a filing, in Europe, we should be in a position perhaps by the end of 2021 to be launching in UC.
As this is a second indication, when then the reimbursement process will be relatively smoother, we'll be probably launching towards the end of that year already, which is two years from now. This is a big feat for the company and a big opportunity as well. In those next two years, you'll see us in France, Spain, Italy, Germany, and the U.K., as I mentioned. Clearly, the objective is also then to grow in the rest of Europe for all our other programs. As I said before, for all our other programs, Europe is exclusive to Galapagos, and we will be then also launching 1690, hopefully, later on in all of those other countries in Europe. We're building our geographic footprint as expeditiously as possible.
With that, let me conclude with two or three more slides on what I would call the outlook for Galapagos as a company and give you a bit of perspective also on the news flow for 2020 before we take the opportunity to take questions on all of the topics that we've had so far today in the presentations. First of all, let's remind ourselves, we're doing this to bring innovation to patients, and innovation is the word that I like to focus on and emphasize as much as possible. 2019 has been a transformative year for us with the Gilead collaboration, and we will be also still applying for approval in the U.S. in RA later on in this year. It's been an amazing year already.
2020, I'll get it back into a bit more detail in a second, will provide news flow on all of our key pipeline assets. It's a very, very news flow rich year next year that's coming to us. Clearly, what's our ambition beyond? Let me stress that one more time. It's a continued focus on innovation. I think today was a fantastic example of how we are innovating from the very early works in target discovery up until the very late works in late development, and that is and will remain the focus of Galapagos. We hope to be doing additional product launches, obviously, and build a European Commercial Powerhouse while doing so. And 2020, more specifically, what can you expect from us in 2020? A lot. First of all, we'll have filgotinib, the phase III start in ankylosing spondylitis.
Very importantly, obviously, for our filgotinib program as well is going to be the data readouts on ulcerative colitis in the first half of 2020, and then the launch of filgotinib probably in the U.S. and Europe and Japan in one year as well. It's going to be a big transformative year again for Galapagos because of all the events around filgotinib. Very interestingly, we haven't spoken about that a lot today. We're waiting for the data obviously to come in the course of, again, the first half of next year. It's going to be our osteoarthritis compound 1972, and that is going to be a very interesting data set phase II-B, 850 patients that we're going to be unblinding in the course of 2020. There's two earlier PoCs, one with G1205 in IPF, and that's the PINTA trial.
Also we have a trial with our autotaxin inhibitor 1690 in systemic sclerosis, and we'll hope to see data with those two compounds in those two indications in the course of 2020 as well. Obviously finally Toledo, Piet pointed out earlier, we're going to be doing a UC study with our pantol 3312, and we're going to be expecting top line data in patients next year. At the same time, we'll be starting with our second Toledo compound G3970 in multiple proof-of-concept studies as well. A very newsworthy rich 2020 and I would invite you to share the joy of the ride with us also next year. Pioneering for patients, that's what we're doing here. We discover, we dare, we care. I thank you for your attention.
Thanks very much to all of our speakers. We're going to go now to the Q&A part of the session. We've got about 25 minutes left for that. I'm very pleased. I'd like to invite our operator, Elaine, now to explain to the callers how they can pose a question, and we'll alternate between the room and the phone. Go ahead, Elaine.
Thank you, thank you.. Ladies and gentlemen, if you would like to ask a question, please signal by pressing star one on your telephone keypad. If you are using a speakerphone, please make sure your mute function is turned off to allow your signal to reach our equipment. Again, please press star one to ask a question.
Okay, we're going to start here in New York with Brian Abrahams from RBC.
Thanks, thanks so much for the great presentation. Two questions from me, one on IPF and one on Toledo. On 1690, I'm wondering what changed to sort of guide this, your evolution and what proportion of patients might be required for the futility analysis? I think before you had talked about maybe one quarter of the patients, now it sounds like closer to a third. I'm just wondering if that reflects any evolution in your understanding of the natural history of the disease or anything you're seeing with respect to the standard deviation or variability around blinded treatment effect in the ongoing study.
On Toledo, sounds like a lot of enthusiasm for 3970 and its potential. How do you weigh pursuit of inflammatory indications versus fibrosis indications given the potential you're seeing from the preclinical studies? And w hat's your level of confidence that TLR1 is what's responsible for the systemic toxicity and that GLPG3970 can be safely given systemically? Thanks.
Hi, Brian. I'll take the first question. I can tell you this is not influenced by any new data or any changes in standard deviation or anything like that. It's fundamentally by us actually doing. These models take time to build, and you want to test them out and make assumptions and try to get to what we call operational characteristics to essentially know how you can protect yourself from making bad decisions, stopping a program that is promising or continuing with a program that is not. That's really what drove it. We're still not far from the quarter of number of patients. So, we're maybe 28 to be honest with you. The number is 28%, but those have to cross the finish line, right?
That's something that we probably initially talked about it without really thinking that, oh, no, this has to be when these people cross the finish line and how many more behind them are in various stages because we take all of these data and put them in our model to help us with the decision. I can guarantee you it is not based on any new information that changed our assumptions for the worse. Not at all. It's just a matter of getting together, putting the program in place and looking at our recruitment rates and how we're doing and when we can deliver that.
Okay. On Toledo first, the question on inflammatory versus other indications. We really want to grab it, develop it, understand it. The science is better understood in the inflammatory area, that's where we're going to push first hard. It's also an area where a number of designs of studies allow you to serve typically faster. That's why we're going to do them earlier. While if you look to OP, osteoporosis or fibrosis, these are long-term studies. That's where we say, let's take the time so that we understand the science as well very good and that we design it right. Probably for those diseases anyway, you're talking six-month studies, 12-month studies anyway. Then you need the chronic tox package. Onto one and systemic toxicity. We only put compounds in the clinic which are safe.
In that sense, and every compound is different. What I've told you as well is that with every compound, the fact that you're more selective, you do something differently. We've been mixing TOL-2 selective and TOL-3 selectives, and we're always surprised because sometimes it works, sometimes it doesn't work. Just being present there sometimes does something which we never calculate, we never measure. It's not too much on the toxicity, I would say, but every compound is different. We test the compound, and then we move forward. 3312 really in the IBD models is the best we've ever seen. While if you look to the other models, it's nicely active, but you need to push the dose, and then you say, "Okay, why not try 3970 which is better fit?" Thank you.
Before we go to the first question on the phone, I just want to remind everyone that we also have Dr. Maher here who could answer questions. He's agreed to stay so that he can answer questions if you have any. You might want to take advantage of that opportunity. Okay, Elaine, we can take the first question from the phone queue.
Thank you. Ladies and gentlemen, as a reminder, to ask a question, please press star one. We will take our first question, please. Your line is open from Mr. Peter Welford of Jefferies.
Hi. Yes, sorry, I was on mute, I think. Thanks for taking my question. Apologies. Firstly, just on IPF, actually a question for Professor Maher. I guess I'm just curious, when you look at the treatment rates you're currently doing with pirfenidone and nintedanib, I guess I'm curious what proportion of your patients you're currently treating with those drugs are, or is, sorry. Equally, have you gradually moved in from sort of severe to moderate to severe to now more milder patients on these drugs? What sort of patients do you typically have to see before you put them on those therapies, and why? Is there any, I guess, underlying effect as to your choice of the drug for those two?
I guess related to 1690 on that, given obviously that this is used, I guess, in combination with existing therapy, I wonder if you could give us some sort of insights as to what the split of your patients would be if you were to enroll in ISABELA, insofar as the two drugs and also naive patients who would be eligible to enroll in ISABELA. Just so we can get an understanding from your perspective of what sort of patient that could be. Thank you.
Thank you. The first part, and anyone that comes to see me, I will start them on treatment because I think the lung is a precious organ, and we need to protect it. My view is not shared by all pulmonologists. Across Europe and the U.S., probably about 50%-60% of patients with disease are currently getting access to treatment. That has steadily increased over the last four or five years as people have got more comfortable with the idea of treating pulmonary fibrosis and the concept of trying to prevent progression. I think as has been alluded to, there is a challenge around tolerability. In some institutions, about 30% of patients on both drugs are discontinuing within 12 months, which does speak to one of the unmet needs, that we need drugs that are better tolerated for longer-term use.
The question about splits in a clinical trial. In my practice, it's about 60% of patients are on nintedanib, 40% pirfenidone. I think we anticipated, based on questions for sites in advance of the trial, that it would probably be a 50/50 split between the active treatments, but there would also be about 30% of patients who wouldn't be on treatment, either because of reimbursement issues or because of intolerance.
We have a question in the back of the room from the Janney team. Go ahead.
Hi, this is Aaron Welch from H.C. Wainwright. I have a question for Dr. Maher. It looks like there's a significant variation in the rate of decline in the placebo groups from IPF trials. I was wondering if you could give us any insights into any kind of baseline characteristics that may influence the different rates of decline and also if any of those baseline characteristics may be disclosed from the ongoing IPF trial.
One has to be a little bit cautious interpreting the different trials because a lot of the apparent difference in the placebo groups is purely statistical. It's dependent on how the analyses have been done. We've now tended to move to mixed effects models, which get over the problem that you'll be missing about 20% of endpoint data at week 52. Historically, some of the studies would use last observation carried forward, and they would impute a zero for dead patients. As soon as you impute a zero, you have a big impact on the apparent rate of decline in the placebo group if you have a treatment advantage. That's why the pirfenidone trials look like the patients progress at twice the rate for the nintedanib trials, and it's purely statistical. Can you enrich a trial?
We would love to be able to enrich a trial. We'd love to be able to pick the rapid progressers. We don't actually have any way of doing it at the moment. Purely by making a diagnosis of IPF, we are enriching as much as we can for the group of patients with the most aggressive form of fibrosis. Once we've done that, we haven't got any better way of then picking the even worse cases.
Thank you. We'll take another question from the phone line, Operator.
Currently have no further audio questions.
Okay, great. We have a question here from Patrick Trucchio.
Thanks. Just first a follow-up question on filgotinib. Can you give us an update on the status of the MANTA and MANTA-RAy studies? Can you tell us how much, if any, of the data from these studies could make its way into the RA label in the U.S. at the time of potential approval? To what extent would this data be available for the sales and marketing effort in the U.S.? On IPF on 1690, can you tell us what the efficacy hurdle is for the futility outcome? Is the expectation for the top-line data, at least the potential that we could see a stabilization in FVC? Finally, can you discuss your level of confidence in the safety and tolerability of combining 1690 on top of standard of care? Thanks.
Okay. Thank you very much. Those are like four questions. All right. Tackling them one at a time. For the MANTA and MANTA-RAy, in discussion with our collaborators, Gilead, we're not really disclosing the numbers. What we are saying is that the both studies, actually, MANTA and MANTA-RAy will be together. Both studies are progressing well. Also we want to say that neither of them are needed to gate filing. We will be doing everything we can to finish them as early as possible, once they become available, then they will be used, whether it will be part during the review process or afterwards will be made available. I'm sorry, I cannot give you more information on it.
I know it's very important. This is something that we've been in discussions with Gilead on, that's what we can say at this point. Regarding IPF, the study is powered, just to remind you, to detect an effect of 80 ml between placebo and drug. That would be regardless of background treatment. It's for the totality of the patients, those who are on no antifibrotic treatment or who are on an antifibrotic treatment totally. The futility analysis essentially is done in such a way that if you have no effect at all on any of these doses, we will be given the signal to stop. That's how it's designed. If there's an effect that could lead to a clinically significant number, and again, there are shades of gray.
What we don't want to see is if we have good effects with 80, that this will give us a false signal to stop, and that's the false negative type of situation. That's how we designed it, and that's what it's giving us. Lastly, regarding the safety. This is actually something that we've been monitoring very carefully, and it was very important also as a way to convince the regulators and convince ourselves first, and convince the ethics committees, that we're very responsible the way we do this, because we went from a very small study to a very large program. The safety monitoring in the study is very robust, both at our level. We review it very carefully on an ongoing basis. I tell you, I get a report every other week on this.
Also we have regular meetings for the independent data monitoring committee that they view the data first when we are present. We present the data to them in a blinded manner, and then they have a closed session where they look at the data unblinded, and they render their judgment whether it's okay to continue or not. So far, I can tell you that I've been very pleased with what we've seen so far. I have no concerns. Actually, the independent data monitoring committee has been giving us the green light every time they met.
Okay. We have another question here in the room. Go ahead.
Thank you. Just two questions from me. One, maybe starting with Dr. Maher. Since you're a part of the FLORA study, obviously, this isn't going to be a statistical response, but could you give us any anecdotal feedback of what you perceived as clinical effect or patient condition with the patients that you did treat with GLPG1690? The second question would be for Piet and Walid. You had a chart up of the pathway of rebalancing the inflammatory, different ways of rebalancing the inflammatory, I guess, phenotype of different cells within the body. I'm just curious, you had one point up there for sphingosine-1-phosphate receptor as a target, and we know you're also interested in repolarization of different immunoinflammatory cells like macrophages.
I'm just curious, of the totality of the evidence that your team's looking at, do you think there's better evidence for modulating a phenotype in vivo or more on towards cell trafficking or sequestering lymphocytes? That was a lot, sorry.
I'll just give my very quick view. You're asking me an almost impossible question. The drug was very well tolerated when we used it in the trial. I think one of the challenges of IPF studies is that we don't have a measure of individual response.
SPC is very good for showing population change. Unlike cancer, where you might expect to see tumor regression with a successful treatment, in IPF, success is stability. Because of the variability of the disease, we will see in some patients stability, and I don't know if that's treatment success or just that patient's disease. I don't think I can honestly answer you except to say it was well-tolerated.
The broader question on our approaches. If we look to the Toledo, because I guess that's where the interest come from. We see the repolarization across cell types. Does every cell type react as quickly? No. If you see across the immune cells, you see it across all cell types, some are a bit more sensitive, and some are less sensitive. It's not that for that program yet, we are at a similar choice there. We have the target. We see across those cells, fantastic data, but not every cell is the same. That's clear. We're still there a bit in our old mode of working. We select a target, we observe, we see good in vivo activity, and we start to run.
Coming years, we'll get much more refined on that, and then select earlier on what type of cells, in what disease, do we really need to hit, zoom in on those cells first, select the better targets for those. That's the plan we are moving towards. If you look to the current programs, in fact, with Toledo, it's across the cell types. That's what I can say, what we see.
Okay, we have time for just a few more questions. I'm going to go back to the phone and see if there's any question. One more chance. Operator?
Thank you. We take a question from James Quigley of JP Morgan. Please go ahead.
Hello. Thank you for taking my question. On the filgotinib program, the psoriatic arthritis and the ankylosing spondylitis trials. Given the black box warning for Rinvoq and the comments from the FDA around the class effect, has this changed any of the recruitment or the feedback from investigators or monitoring required in the trial? Thanks.
Yeah, thank you for the question. The quick answer is no. I think the thromboembolic events have been essentially well-known for some time in this space, and all of the companies have been monitoring these very carefully. Fortunately, these are very rare events, and in the case of filgotinib, they're even several folds even more rare. No, we have not been having any difficulties or any concerns from investigators that I'm aware of around this issue. They're quite familiar with them.
Okay. Question from Graig. Go ahead.
Great. Thank you. Thanks for the great presentation this morning. I've got three questions. Maybe the first two are for Piet and one for Walid. On the Toledo program, I was very interested by the approaches of having a Toledo pan and a TOL-2, TOL-3, and a TOL-selective molecule. Can you maybe walk us through what the incremental advantage would be of just going TOL-3 selective versus TOL-2 and TOL-3? Is there something about TOL-2 that might be potentially, I don't want to say problematic, but what is it about going after TOL-3 selective that might be a better approach? Then I was very interested about your interest in going into the siRNA space and was wondering where the opportunities you see are in going after that mechanism.
Is there something incremental that can be improved upon from the siRNA technology perspective, or is it just an opportunity for the company to go into different diseases and targets? For Walid, just in terms of just coming back from ACR, would love to get your impressions on what the feedback was from physicians on their initial thoughts around filgotinib, and maybe if you felt that there were any takeaways from what their impressions are on the initial experience with upadacitinib in terms of launch trajectory, what they're thinking about their excitement or not about that product. Thanks.
I can go first. The TOL program. Well, there are three targets. We learn as we go. From the way I've been taught, I would by nature go for a selective and say that every day I see my scientists and they have designed a novel selective. It's not that easy to beat that pan-Toledo, that's weekly. It's more than there is one target which is responsible for the activity and all the rest is baggage or lost baggage. No, that's not what it is. They play in concert, and that's why going across the molecules and from one selectivity profile to the other, is not a simple walk in the park, let's say it like that. Each have their properties, their strengths, and we learn as we go.
TOL-3 indeed, if you look to the profile, it is from a scientific point of view, the least interesting because it does what an anti-TNF does currently, a bit more. There are other mechanisms of action with similar profiles. On the other hand, if I can take the last patients off adalimumab, I'll be happy to do that as well, because if an oral does the same, we'll do that as well. In that sense, it's a kind of a low base case scientifically, because if I can take that last patient of injection, I will do that. No problem there, that if we can play that game finally, we will do that as well. Let's be clear. The hope scientifically and for patients, long-term treatment is more in those others where we restore the balance in a better way. Let's be clear.
As siRNA, well, two aspects. One, it's really a logical next step if you look to the platform. That's why we want to do it, and we believe we'll become much more efficient in selecting cellular assays, in vivo models, because for every target, because it's always a long walk in the dark, honestly, to find them. It's always a question, is the compound good enough or is the model good enough? We really spend quite a lot of time, iterations, making better compounds, other things. While with an siRNA, if we would get good at that, normally you should do that easier. Honestly, the limitation is how do you get into the tissue? It's quite, I think well known that for liver, there is no problem to get those into the liver.
When we are interested in NASH, for NASH, this would be an obvious choice. In HBV, I've been impressed. I must say, with what those compound do, is a single injection every month gives you a nice [audio distortion] drop drop within once a month injection. This is becoming competitive, I would say. I worked in that area at the early days, and the field pushed on nicely. It's clear that tissue by tissue, to organ by organ, you will either need to rely on the [inaudible] properties or do a targeting trick to get it there, because by itself, they are going to be limited in terms of drug delivery. Well, it was a question for you?
Yeah. I think what I can say, coming back from ACR, it's really a good time now for JAKs. I think there, the attention on the JAKs and the amount of publications, of course, the launch of UPA carries a lot of sound bites, so to speak, and presence in the meeting. I think also over time, people are getting, or the physicians are getting much more comfortable with the JAKs as a class, and they see the efficacy being really very strong and sustained, unlike some of the concerns that you might have that you would lose effects over time with some of the biologics. Also the safety profile, people are getting more aware and, I don't know if you can say comfortable with it, but at least they're familiar with it, I guess is the word that I'm looking for.
I would say that anything that's good for the JAK class will be great for filgotinib. With our efficacy that's really right up there and a safety profile that is promising to be best in class gives you a best risk-benefit profile, and I think it's a great place to be. We're very excited. I'm looking forward for next year's ACR, where we will be the center of attention, because by that time we should be approved already. I'm really excited to see this class really moving forward and bringing benefits to the patients, because I do clearly see that they make a difference.
All right. Thank you. I think we're going to wrap up for now. I just really appreciate everyone coming in person here to the Westin and dialing in and listening in to our webcast today. If your questions are still burning, you can contact Sofie or myself. We'll try to get them answered for you today. Again, I thank you, and I hope that you have a wonderful day today. Goodbye.