Galapagos NV (AMS:GLPG)

R&D Update

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Nov 14, 2019

Thank you all for joining the Galapagos team for the 10th annual R and D update event at Galapagos. This is, Elizabeth Goodwin speaking. I'm Vice President of Investor Relations, and I'm joined here in New York by Sophie Fontkeisel, Barxilias, Waleed Abhisab, Vic Rink, and about 100 investors and bankers. This year's R and D update marks an important inflection point for the company as we citing new R and 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. And 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 and 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. P. V. Flink will speak on our delivery and R and D, update you on Toledo and share his vision for future proofing our productive research engine. While Lead will cover Filgotinib, he will then be joined by Doctor. Toby Mayer, who will provide a clinician's perspective on IPF today. And then Wally 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 leading us time for Q And A before we wrap at approximately quarter till 10. And at this point, I'd like to invite Doctor. Pete Vicening, our Chief Sciences Officer, to take off. Go ahead, Pete. Thank you, Elizabeth. Good morning all over here in New York. That's all 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 and D over the past 12 months. So for those who are longer with us and for a number of years, you know, every year, we show these 4 key moments in a pipeline, which we believe is one a minimum dose or even more for our long term growth businesses. First of all, key for us is that we keep on looking and finding novel targets. So last year, we selected targets in the inflammation area, the metabolic area, fibrosis area and new disease we added is osteoarthritis. Last year, as well as I'm making immediate jump over a couple of years, we've delivered 5 PCCs to preclinical candidates are in fact that's what we end up at the end of the drug discovery phase. 5 is in fact new record. So you can, 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. Novo mek as of in the fibrosis area. It's a CMI synthetic compound, so the scale up to the first batches will take a bit longer. That will move into the clinic after next year. 4259 is a backup in ours in inflammation pipeline. 1499 as well, I want to spend a couple of seconds later. It's the 3rd compound in the to later franchise, we selected to move into preclinical development. As a unique profile, I'll touch upon that during my talk. And 4471 as well is a backup of 1 of the components in the pipeline. So all in all, 5 PCCs, 3 novel methods of action. So we really keep on delivering sufficient ammunition to grow the pipeline. Leading the pipeline, important for us is that we keep on doing novel proof of concept. So out of these PCCs, a number will reach phase 2 and the premise for this is that one that each of the components reach phase 2, we set up 2 proof of concept. So last year, we set up the 12 5, the Pinta in IPF, LV-sixteen twenty nineteen in Skolodermade, the novel studio. And finally, we believe long term success for you need to keep starting 1 phase 3 every other years. So if you can keep on that that pace will be set up for long term growth. So previous year, we started 2019 this year, partner Gilead started the Penguin Phase III with filgotinib. Coming yet, sulfur compounds will get to that stage. But all in all, if you look to how much double targets, targets to PCCs, PCCs would pop we really maintain our pace and we really set up for long term growth and success. I also always show effect in this the discovery area, only how much people work on here, just to give you an idea and impression on how important diseases are. The inflammation area with the so later project is by far the most important. So 40% of the people in discovery look for a neutral leader every day again. In fibrosis, about 30% of people who are there on complete Novo Mexico's actions, pushing forwards for either lung fibrosis, either liver fibrosis. Then we have the smaller areas, we call this, so inflammation fibrosis are the strategic areas. We typically have as well 2 technical areas currently. We're switching between the digital 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. And Metabolic Care as an effort to start a couple of years ago. It's currently as this height. And so we'll go down in terms of FTEs, but we'll keep on delivering a number of preclinical candidates planned over the coming years. So these are our disease areas we focus on. With the expansion of the organization, we'll probably add 1 or 2 areas so that's but that will come over time and is not a topic for today. But all in all, we keep on being focused heavily on our strategic areas. Portfolio R and D, well, in discovery we have around 30 projects. When I talk to my people in the my friends in academic area, you're running a very hard model because you're stopping in tier 6 projects. That's correct. We stop 6 projects every year that as well gives us a room to start 6 to 7 levels. So 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 to 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, this is a metabolic area. So GLP-forty 59 is a small molecule. Is being orally dosed, and it hits a complete Novomakasov action, which is more focused around how the body handles the lipid So it has nothing to do with HGLT2s, nothing with PD4s or whatever. It's completely something coming out of the lipid area. But my scientist really came to me and said that PT is really a target for type 2 diabetes. It has every promise we need to make it successful. So we believe we are the only company working currently on this target. I'm not going to disclose this. So we've been working for years 1st in Rollins. And our rodent models are in fact completely normal mice we use. We put them for 12 week on what we call a Western Diet, which is high fat high sugar intake. And then after 6 weeks, we started those demise with drugs for 6 weeks. So here, you see the outcome at the end of the 6 weeks, at the end of 12 week of the experiments and 6 weeks of dosing. So what you can see is that effect on the lipids, we always see a very clear drop of lipids circulating in the plasma. That's what's really observed. That's the compound is given the dark green bars. We've included, not the 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 diets of the orange bars are the ones that's been set as well for 12 weeks. But yes, as well picked up quite early is a sustained decrease of body rates. 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. Then as well, finally, those mice, which is mice only. I agree with you. They handle much better, all of the sugar content they're getting. So they're fasting, approximately because that's what we measure in mice. Is much lower than in disease states. So really, by blocking this mathematical action, we see a number of parameters, which we believe are important factors that be just moving into the right direction. Having been working for 3 years almost on minuses guys' time, we confirmed this as well in monkeys. So that's what we recently did. So now we are looking here to diabetic monkeys or older monkeys, and they have all of the symptoms of type 2 diabetes. So there are no healthy controls in this experiment, which we've added in yellow, a box where we combine our drug 459 with metformin. Ideas, if we move in type 2 diabetes, all patients will be unmet morphine and we want to illustrate that we don't block that activity. So it's not the idea immediately that with a single dose, you see an increase in activity just showing the principle when you combine them, patients will do well. Again, on the left lipids there, a nice drop of lipids compared to the disease. In the middle, the body weight change, again, as well, in monkey's the combo seems to be do a bit better in that indeed than metformin. And here, we can measure HD A1c. So the glucose bound to hemoglobin and as well there, we see a nice effect. So that's one of the novel and the first projects in our metabolic program, which all in all, is it limited, but that has stage where we currently are doing toxicities with it. Hope to move it into phase 1 next year and then quickly move to type 2 diabetes patients both as a monotherapy and on top of metformin. But just to give you a glimpse that we do more than just in the foundation and fibrosis updates. Most of you, of course, are waiting for the Toledo updates. I can understand that. So it's the biggest program is discovery, the biggest program in early development. And the whole team keeps on being fired up every day So in discovery MSA, we're learning, getting surprised every day in development, we're moving nicely forward and getting close to the patients. So why are we so fired up on this mechanism action? Well, let me try to explain to 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, which is kept under control by the purple bots tubs which are the anti inflammatory cytokines. Even fortunately, you suffer 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 we call here, the immuno cytokines. So what's happening now with most of current therapies, what we do is we restore the band. So 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 charged. Which will affect to put it nicely into balance of the disease stops. But unfortunately, we will all pay a price at that moment because for the next infections these people don't have a fully powered immune system. And that's what in fact we observe with Toledo and that's why we're so fire dope and so driven to bring this to drugs to patients and to the market, it affects, we again restore the balance. But we see that the effect we have an intact immune system. So these patients or patients in the future when taking the computer compounds. They should be much more ready to cope with infections we all get every year. So that's what tells us that if we can bring this to patients, we should tell you the complete new wave of anti inflammatory drugs here. A bit to lead them. So this is the belief we have some data to support it. So let me show here. So with 3, 3, 12 hours fast compound in the clinic, moving to IBD patients, we really went every layer we can't, we could go to go And also, our service is not present in the call. It's a systemic activity. It's a local activity. So we really went done measures to the compounds in every level, but also measures the cytokines in the codon. So it's not plasma in the codon. You see exactly what I've shown to you on the previous slide is that in those disease models, you see an increase of anti TNF levels, every F Toledo you push it back. And unique here is that indeed the anti inflammatory cytokines like IL-ten disease you see drop So the animals are not well prepared. There are these out of balance and Toledo pushes it up nicely. So according to eligibility, the only approach there in the field that has this jewel mechanism of action, and that will restore the immunity in a way that patients won't suffer from the autoimmune disorder and will be better prepared if there's an infection upcoming. That's why we so far adopted. That's why we maintained the large team. That's why we maintained bringing novel PCCs forward. We have to do in the clinic currently. We have 3312 moving to IBD patients. We have 3970. We start Phase 1 this year, moving to multiple ascending dosing. This compound compared to 3 to 12 shows activity of almost the same dose level across all the models. This is a compound we will develop broadly across indications. So these are a couple of examples. We have much more data but on the joint models. So for TRICC12, we have fantastic activity in IBD, but we need to dose much higher in the joint models. For 3970, it's almost the same dose we're using there. You can see on the left in the CIA model for RA, a nice drop of disease activity on the right and IL-twenty three. Vertical arthritis model also a nice drop of disease activity. So this compound really works in skin, in joints, in the GI tract. Across all of the models and I'll show you this later again. So we have different components there and we keep on improving upon all of their properties. So the family has 3 related targets. The disclosure of the target I said is not for today, so you can keep on guessing and doing whatever you like. But so three-twelve is hitting each of these 3 targets. We call it a punctual compounds. $39.70 is only hitting tool 2 and toll 3. So 43.99 is a toll 3 selective. Shows only the drop of Tina does not show the IL-ten. So it's a bit of a stranger in the family, but you're going to see them push us forward into proof of concept to see how well only this part of the activity as well as working. If then, it's a fantastic deck, we can still decide, but 43, 2019 does not have the full promise. I want to stress that. Of what a 3970 or a 2012 has. As you know, we test these compounds across multiple indication in the autoimmune space, and we go beyond the classic borders of autoimmunity. None of the components don't work everywhere. Of a compound swab, for example, in OA, that's clear, very clear. PT1213170 has very similar profile with the difference that 3970 and it's going better into all the tissues also shows some good activity in Osteo. Probrosis models. Fibrosis has been a surprise for us. We are diving deeper into that and might take the compass into that area as well later. If you fully understand what's happening there. Toll 3, as I said to you, 1499 and 23 selective compound has a different profile. We don't see activity in IBD so that IL-ten is really needed for that activity. We don't see activity in Skidmalls because, again, that's part of the activities for some of the diseases really essential, but in the joint models, For CD99, which is as good as any other components we've ever seen. But we keep on pushing further. We're making tool 2 selectors. We're mixing tool 2, toll 3, we'd always get prices. So but we'll keep on bringing over chemistries overcompens forward, and we'll keep on doing that next year. And then next year, this year, next year, we'll have a patient data, and I'll show you what studies we plan. So for 3312, we'll we'll start a UC study. If that's going well, we develop a compound as well for translators. 3970 will explore much broader. So we'll start 3 ways of studies with fast starts couple of short term pox to validate what we see in animals we can translate into humans will be the classical short term pox in inflammatory disorders. Mid of the year, we plan to start dose ranging. We really want to pick right dose at earlier in the program as well. And we might start some longer term toxicities as well there. And then finally, those other indications which are beyond autoimmune probably will start around year end next year. So they are shifted back also. You really first want to understand fully what is this compound doing across the autoimmune spectrum and move it forward quickly there, but not forget that we also see activity in the fibrosis models. And in the OP model. So those indications are planned. So also for 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 sign is. What are you going to do with the money in which if a quite boring question for me that are you going to do with the money? I just want to find love and Rex is the answer. But we've been thinking for a long term How can we do things better? Because working on the negative actions, we had a limited pool of genes that we're targeting how and what's the smart way to expand here. So I want to share with you our plans there as well. So our current approach in drug discovery has been for 20 years the same. We find novel targets. We direct them. And when we have a sales rep within the clinic, we do proof of concept and when the proof of concept is fantastic, but it can take us further into phase 3 and those ranges and we bring to the market. We start to sell. It was a very simple three step approach. One of the limitations we saw over past years is that Finding novel targets in that selected pool of 6000 draggable genes was becoming hard and hard. So, the beginning, we had 50 and then 10 teach 3. So we start to do, say, well, this pool probably It's a bit too small. So first that we're going to do is really enlarge the pool and not going to the draggable only, but to the protein coding, genome, so we'll expand our pool from which we're going to start fishing. This is one of the risks you start to expand the pool. The risk is that at the end of the screening, you're looking to a galaxy of volt targeted light in the open, you have no clue how am I going to start here? So what we need to do to keep signs on track there is to really, as well, develop the partners. So the partners tell us, in fact, Vivendi hold different or some of those novel targets might be connected to science, you know, might be, interlinked as well. On the left you see here, if you just work on other targets and sometimes it is scary picture, I can share that with you that for some of those targets we discovered, we have no clue how this is going to work. Even then some plastic store, but these are really the very difficult and the slow moving programs. If you have an idea on which part where they're working, drug discovery efforts will become really much more efficient and you have a goal in mean and a way to move forward. So you really want to map this much better out a lot of them and wait for others to bring us the map. But the effect you really want to approach is that you have to complete disease network. So you want to understand what's happening to 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 notes 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. So we're going to much more focus on mobile 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. To those pathways, that's something I've invented to give a short chunk here, we expect partridge is what we've learned over the past years, how it works in patients. So if you look here, if you would take an old school book on autoimmune disorders, they would order them by tissue. You will have the disease of the joint together. If you have had the disease of the skin together, you will have the diseases. Of the GI together. And the vascular is a group on its own. After developing multiple drugs, in fact, we've learned that to better group them by pathway. Some of these diseases are sensitive to IL-twenty three, similar to IL-seventeen, but there's a difference between IL-six and IL-one. So 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. So we're really going to add to the whole system a level of patient data. So recent years, the technologies have become available that allow you to look 3 levels lower than what we did until now. Let me give you an example. Here's these are how we today look into the joints of RA patients. We've always worked with tissues out of our hip, our hip patient will be took the tissue as a whole and look to the mix issues. Today, we're seeing the cell sequencing. You can degraded tissue up to a single cell level, then you're going to sequence a couple of 1000 cells. And now you can cluster those cells according to their gene expression into functional types. So you can separate out the monocytes, the T cells, the B cells, the fibroblasts delivered. And you can measure the amount. That's the first, that was an easy level. You can go a little deeper. If you now look to what JAK is in all of these cells available, because they've saved ourselves 10 years of debate between JAK1 JAK2 and JAK3. Only one jack, which is present in all of those cells. So if you really want to block in the joints, I have 6 signaling, but choice is made in immunity. So by looking into those cells, how they're active and how the different cell types work to come to the right choices, much more quicker than we ever did today. Well, Vintrust is a bit the blue gray clustering there where people in fact never talk about when we talk about our truck in our community. We talk about T cells and B cells, and that's how difficult it is. We never talk about the fiber plus. So you have different types of fiber loss. Really because informative, you can now cluster these or you can bring them back to how a joint really look like. So few four cores for the 4 different types of fiber blasts. I can see it, you have a green, a red, orange and a blue, So one type of fiber as you see, the lining. 2nd layer is blue one. You have the red ones which are in the blood vessels, and you have the green one should are just around the blood cells. So 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 RA 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've always been I not always, we've been we are extremely proud on our small molecule platform, but we've always also had a couple of targets where we blocked the enzyme and nothing happened in the disease where we could not block the enzyme where it was a target is doing everything right that we don't find the way to modulate. So we're going to, as well, expand on the type of direction we want to develop. Let me explain it quite simple. Industry always worked on the right of this cartoon. We always made compounds that act it or blocked organ. So these are the small molecules that has been the origin of this industry has been the focus. They have supplement that with peptides and antibodies cell therapies between all restaurant on the right hand side. In theory, for every target we direct 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 sRNA or an antisense. 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 is a piece as well, you in theory could have a good type of novel drugs. So what have we selected out of these modalities? So we've highlighted them in orange, So we will keep our regular small motors. So don't panic and run out of the room. They're going to change everything, but we're going to build further on our expertise. First, we're going to add on what we've been working on in the lab for a number of years. It's to as soon as we have bind those 2 to proteins direct those binders to the enzymes that degrade or the solar components that degrade proteins and so on. So that's what they call the products. Also can do the inverse trick what we learned in the CF area. You can add compounds that influence the confirmation of a protein. So the protein is much more pro drawn to, to the enzymes. On the other hand, if you see what our platform does, our platform, in fact, is a knockout our knockdown platform. We're knocking down a target. So we are going to invest into, as I RNA, 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 an overview, we'll keep on doing small molecule discovery. Don't worry. Those targets where an inhibitor on activator doesn't work, we're going to use other tricks to degrade the amount of protein. It's going to be, I'm first wave. The product is late for small models, because it takes time to build up that form. And then finally, in order to also much more efficient drug discovery is going to do as RNA type of going to bring in as RNA type of work. To really from our knockdown platform, immediately map the pathways, immediately select models so that we're much faster can can, select out the promising targets and the drugs. And eventually, if you're good enough, even bringing as RNA to the market or to the clinic ourselves. So that's the expansion we are planning. We are actively looking and searching. So we're going to build, collaborate, acquired 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 6000 genes. Year, we get more or less 6 more virtual targets out of that. And that translate then into 33 PCCs on a yearly basis. Currently, if you look on how we plan the organization, Over the coming years going to expand the pool from 6 to more than 20,000. We'll have more hits. So we'll need the part ways to guide us. To help us selecting the targets. But with siRNA and all of that, we can take a number of targets immediately to the right track here. Anyone does well have more, starting points for a small molecule. So ideas will be able starting more small molecule programs and deliver more PCCs either as a classic small molecules, either as a protect that degrades the proteins either as IRAs that inhibit the formation of the proteins. There are also 4 for my talk. And I now invite Ollie, it shows us on figures and our latest use. Hey, good morning, everybody. Good afternoon for some of you who are on the phone joining from other parts of the world. Thank you Pete for walking us through these early part. So 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's, essentially profile and its risk benefit profile has been becoming more and more crystallized with every new data that we get. As you know, earlier, the 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. This is our both study, 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 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 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 market inflammation is expected to be by 2027, which we're talking about $65,000,000,000. And 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 And then 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 1st 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 psoriasis arthritis, we're getting ready to move on in to the Phase III program. This is a disease with a high unmet medical need. These are, 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. And 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 this trial. This was a trial of about 65 patient per arm, so 130 total, given filgotinib 200 milligram or placebo in a 1 to 1 ratio treated for 16 weeks. And you can see the ACR 20 response here are in the upper 80s, ACR 50, more than 50% and even ACR 70 in the short duration in these more difficult to treat type of population is getting close to 30%. These, these data look very promising. And based on that, we continued development of this compound. Just recently at ACR, we shared the data from the long term extension of this trial. So at the end of those 16 weeks, those who are on placebo will get given in an open label fashion Filgotinib 200. And those who are on Filgotinib 200 will continue their treatment. And 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. But also the safety story continues to be as impressive and consistent with what we seen before. On the left hand side, these are the safety, that we're seeing in the 1st 16 weeks of treatment with you know, filgotinib and placebo so he can compare. And we, here, we selected the adverse event of of interest like serious infection, opportunistic infections, softer, DVTs and so on and so forth. And 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. So no, no DBTs or PEs no additional death. There was one additional maze, maybe a couple of serious infections. And what you see on the right hand graph for these facility 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. And 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 really has been very 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. So let's talk a little bit about the Phase III program that we're moving forward, with an inkylosing spondylitis. It's called Penguin. It's going to be, similar to our RA program at high level in that, we will for both doses of Filgotinib, 10200, Penguin 1, high level, it looks like FINCH 1, if you want to. This is in metatrexate 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 would be 2 doses of filgotinib. And, and 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, but if they were on placebo or adalimumab, there would be re randomized filgotinib 100 to 200. And 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. Sigmund 2 is the in the biological IR population. It will be 2 doses versus Placebo. The double blind portion of the study will be 16 weeks, primary endpoint will be at week 12, and primary endpoint, by the way, for both studies will be ECR20. And again, at the end of the 16 weeks, the patients who are on placebo would be re randomized to Filgotinib 200 and those who were on 100 to 100 will continue in a blinded manner in terms of treatment dose assignment. So 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 Pete talk about it earlier today as well. About how we go about looking at these things. So from the get go, our hypothesis was, you need to block JAK1 that 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, we, you're now starting earning off target activities and increase in side effects. And we designed Filgotinib specifically with that in mind. And 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 McKinney and others that have been published. That our compound has been highly selective for JAC 1 versus JAC 2 in the left hand side graph and also highly selective JAC 1 versus JAC 3. And the right hand side graph, which with about 25 fold in both cases. So this is specifically designed so that you 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 Jack 2 or Jack fee and stay away from any liability. And 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 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. And also we work across the board, whether you have, early RA and you're naive to Massachusetts state, whether you are methotrexate incomplete responder or even on the other end of the spectrum, biologic incomplete responders. And as a matter of fact, we've also shown recent some sub- some group analyses at ACR, where it doesn't matter whether you're, you've been exposed to 1, 2 or 3 previous or 3 or more of previous biologic and you have not responded, your response to Filgotinib is the same. So very robust, very sustained efficacy, and you see it very early. Importantly, this comes without additional liability of target activities. So these are the data summarized the safety of some key important elements that if you think about the Jack class in general, people have raised questions, well, we were not sure a little bit about the risk, increased risk serious infections, increased risk of herpes, or increased risk of thrombo embolic events, well, here they are. These are data from our FINCH program, more than 3500 people, more than 2000 exposed to Filgotinib on the far right hand column. You have the people on, adarimumab in the middle about 300 patients. And those on the left are the placebo and methotrexate active treatment from FINCH 1 FINCH 2 FINCH we lumped together for about 1000 patients. And 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 and they look very competitive when you look at the 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 study. This is a long term mention 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 and ACR. And you can see up to week 156, we have more than 22,200 patient year exposure. And here, I'm showing the data in event per 100 patient years. Again, you see these rates for serious infection, Zoster, DVT's PE and death. The rates are quite low. Pointer retention for DVDs and PEs. I'm sure you've spotted it as well. The rate is at 0.1 and this is very, very low if you've been looking at data from other, 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 signs 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 normalize certain laboratory parameters that are abnormal inflammation specifically, I'm thinking about, hemoglobin changes and platelet changes. And in addition, it has a clear safety profile, which is in our opinion, a result of this high selectivity. And you see that across the board and continues to be confirmed the more data we add So I, with that, I'm going to finish my talk on Filgotinib and switch gear. And actually, we are very fortunate today to have with us, Professor Toby, who has been actually with the program, 1690 longer than I have, since he's been involved in the design of the, 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 Isabella and lead program, delete 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. So, Professor Mar, he's a professor of interstitial lung disease at the National Heart And Lung Institute at the Imperial College in London, He's also the director of Respiratory Research at the Royal Brompton Hospital in London as well. And we've been very fortunate to be working with him, for the past several years and any more to go. Toby? Waleed. That was far too many words about me. But I'm going to talk to you about idiopathic pulmonary fibrosis, which obviously has been a large focus for Galapagos over recent years. To tell you a little bit about myself in my own words. I work here at the Royal Brompton Hospital, 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 and the lady there, Dane Margaret Turner Warwick, actually set up our lung fibrosis unit in these a long time before anyone else became interested in fibrotic lung disease. As a consequence, I currently or my service currently looks after about 1500 new with pulmonary fibrosis each year. We have about 5000 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. So we've got extensive background in running clinical studies. And as Waleed said, I got to know Galacas. I think it was 2013 or 2014. So a fair while ago now. So what is IPF? So IPF is a progressive scarring disorder of the lung, it tends to affect older adults in many ways, you can think of it lung equivalents of Alzheimer's disease. It's the lung prematurely aging in advance of the rest of the individual. And as the lungs scars, it becomes less effective as an organ of gas exchange. Obviously, our lungs are working to get oxygen into our body, carbon dioxide side out of it. As that scarring process progresses, people become restless they ultimately slip into respiratory failure and ultimately they die as a consequence of their disease. It's a pretty nasty condition to have. Without treatment, the median survival is about 2 to 3 years from diagnosis. 5 year survival is around 20%. And the graph here just compares the 5 year survival of idiopathic pulmonary fibrosis to a variety of cancers. And I think one thing to notice is that the 5 years 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. And moreover, IPF has a prognosis very similar to adenocarcinoma of the lung. So whilst it's not a malignant disease, it has an outlook akin to malignancy. What's important is that it's becoming more common. So at the moment, FDA, European Medicines Agency consider IPF to be an orphan disease. Truth be told, it isn't. Then the United Kingdom, one in every hundred people who dies dies as a consequence of IPS. Same is probably true in the U. S. Probably 100 of us in this room, at least one of us is going to go from IPS. So probably not an orphan disease, but we won't tell the FDA that. At the moment, there are probably, 40,000 to 50,000 new diagnoses of IPF in the U. S. Each year. Are probably 250,000 or more people living with the condition as it stands. As I 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 effective than women probably because of past smoking habits and also because of exposure to dust in the industrial setting. That said, IPS 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, so about 5% to 10% of our patients will have a family member who's also suffered with pulmonary fibrosis. And 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 lungs. So obviously, we're breathing in 5 liters of air every minute. That air contains dust It came to other people's cigarette smoke. It contains viral and bacterial particles, and all of those things are causing little bits of damage to our day in, day out. And it seems there is a threshold at which once you increase the level of damage that you experienced during a lifetime, you become more likely to develop IPS. And then the final piece of the jigsaw is getting older. And I think those factors are important because we are seeing that the disease increase in incidents. 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 micro particles, diesel fuel, which may well be triggering damage that leads to fibrosis And 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 IPS. But anyway, once the disease triggers, we see activation of multiple pathways involved in the normal wound healing response. And that leads to fibro proliferation 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, there'll be oxygen dependent. And 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 center 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 force vital capacity, which is a measure of of lung volume, 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 force majeure capacity every day for 18 months. You can see the gradual rate of progression in his disease. He'd about 10% of his lung function in 12 months. This is another individual, much more rapidly progressive disease. He died 2 20 days after entry study. And then this is the 3rd pattern that we see. So this patient had an acute deterioration and actually patients with pulmonary fibrosis are uniquely susceptible to lung injury. So when they develop something like an infection, they get wide red inflammation and damage of the lungs. And once 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 1 in 20 of our patients each year and are one of the leading causes of death that we see. We can use 4th cycle capacity, to understand disease progression in the individual patients We've also used force cycle capacity to help develop better trials. And the FDA are now very happy with using rate of change in force vital capacity as their primary endpoint of choice for approval studies in IPS. Just, I want to keep hammering home how bad this disease is. So in case you haven't gotten a 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. So if I see 100 new patients in a month, I can pretty much work out what will happen to them over the next 3 to 5 years. Unfortunately, people still present quite late with this disease. So even at diagnosis, about 15% patients will already be oxygen requiring. If I go a year down the line, during that 1st year, we have some of those patients with very rapidly progressive disease, about 20% of patients will be dead by the end of 1 year, and some of the remainder will have slipped into respiratory failure. After the 1st year, the death rate sort of settled down at about 15% a year, which means that by the end of year 3, half the population are dead and a proportion now oxygen requiring. And if we fast forward to 5 years, somewhere around 20% of my patients will still be alive 5 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. So we have seen the developments of treatments. There are 2 FDA approved therapies. There is Pefenadone, this was the pivotal trial that showed that percent of loans slows the rate of disease decline as measured by SCC by about 50%. And then the other drug is Nintedinib, again, a similar magnitude of benefit in terms of slowing FCC decline. Those drugs were both approved in late 2014. So we've now got 5 or more years experience in using them. And 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, you normalize for baseline disease severity, there appears to be an improvement for patients beta with anti fibrotic drugs. But I'll highlight this graph here. So this was, some work we did with, data available from open labeled trials of patients on Percenadone. And these patients have been on treatment for 10 years or more. Comparing them to historic severity matched patients, we found that percent of them probably gives 2 years extra life expectancy to our patients. But the 3rd line on the graph is the normal life expectancy for the average sixty seven 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 to 15 years. So 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. And then 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. So whilst we focused on idiopathic pulmonary fibrosis as the worst of the fibrosine lung diseases, we actually, for every one of our IPF patients, see 2 other patients with different forms of fibrosis. So it can arise in the context of connective tissue disease, so rheumatoid arthritis, systemic sclerosis, And we also see a range of other conditions, things like asbestosis or chronic hypersensitivity pneumonitis. And all of these core scarring of the lungs and the majority of them go on to cause death sometime a little more slowly than with idiopathic pulmonary fibrosis. But this was the data from the pivotal study done with nintedinib in patients with scleroderma associated ILD. And the FDA have now approved Nintedinib 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. So as Wally said, I was fortunate enough to, be involved with the FLORA study, the Phase 2 study of GPLG 16, 90 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. But this was us presenting the data at the ATS meeting a year ago. And Waleed, I think, is going to talk. To the results in a second. So I'll just wrap up. These are pictures of my patients attending open days that we held I'm 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. Is becoming increasingly common. We've shown with Perfenodone and the Intetinib that fibrosis can be treated and there is a pathway to approval, but 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 in this disease. Very good. Well, thank you, Toby. It's a very sobering talk, but at the same time, it's also very motivating for those of us who are working on the studies. As you know, Galapagos really is putting IPF in its crosshairs and we have a number of approaches try and tackle the disease. So, 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 FDC decline by about 50%, the problem is also that they have some tolerability issues. And in real world settings, about a quarter, the patients do not take these medications, and they discontinue about at a rate of about 25% per year. Because they don't tolerate it and they don't see effects from it. Despite that, the market size in 2018 was more than $2,000,000,000 for these drugs for fenidone and intenet. So maybe by a little bit of background, just bear with me. I'm just going to walk you through a bit our story there. So where does how does 1690 work? So we need to take a step back and look at the auto tax and as a target. So on the left hand side of the graph, you see a cartoon, which is taken from a New England Journal paper by David Letter where he was reviewing the various negative actions of these compounds. And you can see the pathway that we're talking about here highlighted. So, the auto tax and enzyme is widely expressed it is responsible for converting lysophosphatidic choline to the bioactive lipid lysophilic for synthetic acid, which in turn then works through a number of different receptors of at least 6 g protein coupled receptors. To produce its activity. It's expected, it's known to essentially regulate diverse cellular process such as proliferation, differentiation and migration. And these have been involved and have been linked to a variety of disease particularly in inflammation and fibrosis. So one of the things about 1690 is that it has a dual role, in the way it blocks, auto attacks. And so essentially, it blocks the type 4, enzyme. Is not only responsible for blocking the enzyme itself, but it also blocks the transport about VA1 as forms. So it has to do a mechanism of action. Which is, which we expect that it will render it much more potent in controlling LPA levels. And based on that science and there's a lot more, which I'm skipping over, that were done in Pete'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 16.90 at 600 milligram once daily over a period of 12 weeks. This trial was randomized 3 to 1 drug versus placebo. And we looked at a number of endpoints, including changes in LPA levels in the blood. And, in addition, we looked at FVC. And the study was not powered to detect changes in FDC because of the size of it, it was mostly designed to look at safety and tolerability as well as pharmacodynamic effect, but we were very surprised by what we were able to see, which you can see here on the graph, but it seems like stabilization of the lung functions and patients receiving drug. And about at the end of the trial, 12 weeks, there was about 100 mil difference between drug versus placebo, in this office space spirometry. Actually, those data was were corroborated by home based spirometry, and you can see these data in the lasset paper that was published, where also the difference over time was about 100 mills between the 2. When you couple that with the clear effects that we've seen on imaging, we used a functional respiratory imaging where we show where we showed that the drug essentially stabilizes the disease completely as opposed to the placebo patients who continue to decline and a safety profile that looked very promising we were very excited to embark in further development of this compound. And as we are moving and preparing for it, we had a very nice surprise. And that, BMS actually validated, the, the auto tax pathway in patients with IPS. 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 LPA 1 receptor, and this is a compound by BMS. It said it was put in a double placebo controlled trial, which was a reasonable size, about 50 per group. So 150 patients total treated for about 6 months. And you can see very nicely on the graph on the right hand side, a dose dependent effect, in reduction in FVCs decline over this time, reaching statistically significant 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 and animals, and they are continuing now its development as far as I know. So what does our developed program look like? So this program is made of 2 identical trials, each comprising 750 patients that would be randomized in a 1 to 1 ratio to Placebo or 2 doses of 1690, 200, or 600 milligram once daily. The patients will be virtually all comers. So essentially, patients who are on standard of care are welcome, whether that includes antifibrotic therapy as in profanity donor and intenib or on neither of them, but they are on some supportive care. Or for whatever reason, they're not on this medication, that are allowed to come in. We expect in the end, and that's what we target to about, to have about a third of the patients on the fenidone, about a third on the intatinib and it serves on neither of them because that is how, how, the situation is in the Western world, the U. S. And Because we're going on top of standard of care, we can't afford to keep the patients on their randomized treatment even after the primary endpoint at V52 until the last patient crosses the 52 week line, which means everybody else would have gone much longer than that. If you think of about 1.5 to 2 years of in life, part of the study, so some patients would have been on this up to even 3 years. And 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 hospitalizations due to respiratory failure. And 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 IPS. 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 what they will see in the clinic, but also will generate not only data on the primary endpoint, which is FDC, which is a regulatory accepted endpoint, but also generate data on these important endpoint, that such as death and respiratory, hospitalization. On top of that, we will have large safety data that in 1500 patients, but not only for a year, but also for a much longer period of time. So 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 addition, I should say to our, to our sites. After having discussed the plan and agreed to it with the PMDA, we're very happy now to start in Japan and 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. And 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, very nicely. This gives you a little bit of the timeline that we have we're very happy to say that we are a third of the criteria so far. So we have 500 patients on Thrive, over the 1500. This is ahead of, 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, very favorable. We've also talked about the need to do futility analysis, because again, we jumped from a small study to a larger program. We want to make sure that, if the results in Florida were completely a fluke and the drug doesn't do anything that we stop the program, before without before we go all the way all the way out. In order to do that, we, did a robust analysis of statistics 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. And in doing so, we, reached the conclusion that we need about a third of the patient or about maybe 30 percent of the patients to clear week 52. And with that totality of the data, we will have enough information to make that decision in a wise way. So it's really a robust, futility analysis that we plan to conduct. So we have reached this target, we think of the patient recruited now. Now we need to get them through the trial. So we expect by this time, year should have enough of the information that we need, then we need to bring the data in, analyze it, have it go through the independent data monitoring committee, So we expect that we'll be able to communicate on this in the first quarter of 2021 or early in that quarter as well. And, 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 the 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. So I expect that we should be able to communicate top line results in the early part of 2022. And, with that, I think I've covered all that I wanted to cover around IPS and Filgotinib earlier, and I'll turn it over to Bart to tell us a little bit about how are we 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. Now this slide is familiar to familiar to most of you, I would say, but I think given the sizes, but as the complexity of this transaction, I think it's worthwhile to highlight a couple of aspects here. So first of all, our transaction that we've signed will give you the last in 10 years. And as a result, it provides Galapagos a very important time period of independence and ability to invest in our own R and D platform with all strengths that Pete and Waleed have been showing earlier on this morning and allowing to, to build that forward, on a stand alone basis. It's also important from a financial point of view. We've received $4,000,000,000 of up funds for the transaction that we've signed in July. Received this in August. And 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 programming 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. And then there's further opt in options when programs achieve the end of phase 2, in our pipeline. So significantly also in terms of cash, Also, an equity investment, this number has gone up since a previous slide that you've seen because Gilead has had also the right to to increase their stake to a level of 25 percent by the exercise of a specific warrants. That warrant has been exercised, meanwhile, and last week. They've increased their stake to 25.1 percent. I think we've issued a press release on this, as well. And the total amounts received for the equity investment is now $1,500,000,000. And then finally, and that's obviously a key key component of the economics of our collaboration with Gilead. That said, we are receiving royalties on all our products that start at 20%, they go up to 24%. And that's obviously a very meaningful percentage. So in case you're wondering, is there future exposure economically to the U. S. At Galapagos? The answer is definitely yes. We've received royalties on all of Gilead 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. Here, we retain all of Europe for Galapagos during the collaboration for all our programs. And 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. And 1st in Europe, And then you never know down the line when we'll make the shift also to the U. S, but first, we're focusing clearly as part of this transaction on Europe, And 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 3 out of the 5 EU 5 countries. So Spain, France and Italy will be launched in RA by Galapagos, whereas Gilead will launch in Germany and the UK in RA. And we've swapped our territories for our subsequent launches. So when we go to IBD, 1st in line will be UC, we will be launching in Germany and the UK and Gilead will launch in Spain, France and Italy. And not on this chart, but the Benelux has always been part of the exclusive territory for galapagos. So we'll be launching all indications in Galapagos. So 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 interests of the molecule. When 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. And at the same time, it allows both companies also to book revenues in all of these territories. So we will be the revenue booking entity for Spain, France, Italy and the Benelux, whereas Germany and the UK for all indication sales, revenue will be booked by Gilead. It will also really allow us to build our infrastructure in a phased manner. So the focus clearly now is on those 1st 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 UK. And as the RA lead company in those countries, we will be also responsible for the physical distribution. We will also be the party who will negotiate and execute on access negotiations with governments. So we are really in full launch mode with filgotinib as we speak. And that's important because obviously time is is short until actual launch. We hope to have an approval in Europe in the second half of twenty twenty. So 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 1st country in RA launch, will be executed perfectly. And 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 for a while. Obviously, we are, bringing this forward. We're working on the access. We have all the access teams in place and we're building things like the physical supply chain and all the support functions as well. And then as I said, UCBIL, us a bit of extra time for Germany and the UK, but not even that much. Earlier, you've seen that we expect the data and you see in the first half of twenty twenty, if you then roll forwards with a filing in Europe we should be in a position perhaps by the end of 'twenty one to be launching in the UC. And as this is the second indication, when then the reimbursement process will be, be relatively smoother. We'll be probably launching towards the end of that year already, which is 2 years from now. So this is a big feature for the company. A big opportunity as well. So in those next 2 years, you'll see us in France, Spain, Italy, Germany and the UK, I mentioned, but clearly, the objective is also then to grow in the rest of Europe for all our other programs. And as I said before, for all our other programs, Europe is exclusive Lucalapagos. And we will be then also launching 16090 hopefully, later on, in all of those other countries in Europe. So we're building our geographic footprints print as expeditiously as possible. So with that, let me conclude with 2 or 3 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. So 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 also still, applying for approval in the U. S. In RA later on in this year. So it's been an amazing year already. 2020, and I'll get it back into a bit more detail in a second. Will provide news flow on all of our key pipeline assets. So it's a very, very news flow rich year next year that's coming to us. And then clearly, what's our ambition beyond, let me stress that one more time. It's a continued focus 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 developments, 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 3 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 twenty twenty. And then the launch of filgotinib probably in the U. S. And Europe and Japan in 1 year as well. So it's going to be a big transformative year again for Galapagos. They're because of all the events around Filgotinib. Then very interestingly, we haven't spoken about that a lot. Today, we're waiting for the data obviously to come in, in the course of, again, the first half of next year, is going to be our osteoarthritis compound 1972. And that is going to be a very interesting data set phase 2b 850 patients that we're going to be unblinding in the course of 2020. Then there's 2 earlier books 1 in 12 of with 1205 in IPF, and that's the Pintech trial. And then also we have a trial with our auto taxi inhibitor 1690 in systemic sclerosis, and we'll hope to see data with those 2 compounds in those 2 indications in the quarter of 2020 as well. And then obviously, finally, Toledo, Pete pointed out earlier, we're going to be doing a UC study with our pan sol 3312, we're going to be expecting top line data in patients next year. And then at the same time, we'll be starting with our second Toledo compound 3970 in multiple proof of concept studies as well. So a very new store reach 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 And 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. Thank Okay. And we're going to start here in New York with Brian Abrahams from RBC. Thanks and thanks so much for the great presentation. Two questions from me, one on IPF and 1 on Toledo. On 16 90, I'm wondering what changed to sort of guide your evolution and what portion of patients might be required for the futility analysis. I think before you had talked about maybe 1 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 standard deviation or variability around blinded treatment effect in the ongoing study. And then 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 what's your level of confidence that TOL-one is what's responsible for the systemic toxicity and that 3970 can be safely given, systemically. Thanks. Brian, I'll take the first question. So I can tell you, there's this is not influenced by any 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. 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. But that's really what drove it. You know, 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? And 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. So I can guarantee you it is not based on any new information that changed our assumptions for the worst. 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. A little first, the question inflammatory versus other indications. It's a new concept and We really want to grab it, develop it, understand it, and the science is better understood the area. So that's where we're going to push first the heart. And it's also an area where a number of design of studies allow you to serve typically faster. That's why we're going to do them earlier. Why if you look to OP or Porosis are fibrosis. These are long term studies. So that's where we say, let's take the time so that we understand the signs as well. Very good and that we decide it's right. But probably for those diseases anyway, you're talking 6 months studies, 12 So it's anyway. So, and then you need the chronic tox package. We only put compound in the clinic, which are safe. So, in that sense, and every compound is different. What I've told you as well is that with every compounds, the fact that you're more selective should do something differently. So we've been mixing toll 2 selective and toll 3 directives. And we're always surprised because sometimes it works. So that does work. So just being present there sometimes does something which we never calculate, we never measure. So it's not too much on the toxicity. I would say that every compound is different. We test the compound and then we move forward. Since it was really in the IDD models, it's the best we've ever seen. So While if you look to the other models, it's nicely active, but you need to push the door and then we say, okay, why not trying 3970, which which is benefited. Thank you. Before we go to the first question on the on the phone, I can want to remind everyone that we also have Doctor. Meyer here who could answer questions. He's agreed to stay so that he can answer questions if you have any. So you might want to take advantage of that opportunity. Okay, Elaine, we can take the first, the first question from the phone queue. Thank We will take our first question please. Ed, your line is open from Mr. Peter Welford of Jefferies. Yes, sorry. I was on mute. I think thanks for taking my question. Apologies. Firstly, just on the IPF, actually a question for Professor Meyer. I guess I'm just curious when you look at the treatment rate you're currently doing with profenidone and an entinib? I guess I'm curious what proportion of your patients you're currently treating with those drugs are or is sorry, and equally, have you gradually moved in from sort of severe to moderate to severe to now more milder patients on these drugs? Or what sort of patients do you typically have to see before you put them on those therapies and why? And is there any, I guess, the line effect as to your choice of the drug for those 2. And then I guess related to sixteen ninety on that, given obviously that this was used, I guess, on 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 enroll in Isabella, in Sabadra as the 2 drugs and also naive patients who would be eligible to enroll in Isabella, just so we can get an understanding from your of what sort of patient that could be? Thank you. Thank you. So 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. But my view is not shared by all pulmonologists and across Europe and the U S, probably about 50% to 60% of patients with disease are currently getting access to treatment. That has steadily increased over the last 4 or 5 years, as people have got more comfortable with the idea of treating pulmonary fibro and the concept to kind of prevent progression. I think as have been alluded to, there is a challenge around tolerability And in some institutions, about 30% of patients on both drugs of 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. And the question about split in a clinical trial. So, in my practice, it's about 60% of patients from Nintedanomics 40%. Pennadone, but I think we anticipated based on questions, the sites in advance of the trial, it was probably be a fifty-fifty split between the active treatments, but there would also be about 30% of patients who wouldn't be on treatment either of the 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 Doctor. Marj. So, it looks like there's, significant variation in the rate of decline in the placebo groups, from IPF trials. So 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, the Encoin IPF trial. Cautious interpreting the different trials because a lot of the apparent difference in the placebo groups is purely statistical. And it's dependent on how the analyses have been done. So we've now tended to move to mix the sex models, which get over the problem that you'll be missing about 20 percent of endpoint data at week 52. Historically, some of the studies would use last observation carried forward and they would impute a 0 for dead patients. As soon as you impute a 0, you have a big impact on the apparent rate of decline in the placebo group if you have a treatment advantage. And that's why the profenolone trials look like the patients progress at twice the rate for the nintedentib 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 rapid progressors, but we don't actually have any way of doing it at the moment. So essentially, 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 But 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. Okay, great. Let's say 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? And can you tell us how much, if any, of the data from these studies to make its way into the RA label in the U. S. At the time of potential approval and to what extent would this data be available for the sales and marketing effort in the U. S? And then on IPF on 16 90, can you tell us what the efficacy hurdle is for the futility outcome is the expectation in the, for the top line data, at least the potential that we could see a stabilization in FDC And then finally, I guess, can you discuss your level of confidence in the, safety and tolerability of combining 1690 on top standard of care. Thanks. Okay. Thank you very much. Those are like 4 questions. That is one at a time. So for the Manta and Manta Ray, in discussion with our collaborators, Gilead, we're not really disclosing the numbers. So what we are saying is that both studies actually MANTA and MANTA Ray will be together. Both studies are progressing well. We're happy with with the progress, but also we want to say that neither of them are needed to be, to gate filing. We will be doing everything we can to finish them as early as possible. And once they become available, then they will be used, whether it will be part during the review process or afterwards will be made available. But I'm sorry, I cannot give you more information on it. I know it's very important, but this is something that we've been in discussions with Gilead on, and that's what we can say at this point. Regarding, IPS, so the, the study is powered, just to remind you to detect, an effect of 80,000,000 between, between placebo and, and drug. And that would be regardless of background treatment. So it could be it's for the totality of the patients. Those who are a no anti fibrotic treatment or who are anti fibrotic treatment, totally. And the futility analysis essentially is done in such a way that if and if you have no effect at all on any of these doses, we will be given signal to stop and that's how it's designed. But 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 kind of the default a false negative type of situation. That's kind of how we designed it. And that's what, what'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 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 So 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. But also we have regular meetings for the independent data monitoring committee that they view the data First, when we present, we present the data to them in a blinded manner, and then they have a close session where they look at the data unblinded and they their judgment, whether it's okay to continue or not. And so far, I can tell you that I've been very pleased with what we've seen so far. I have no concerns. And actually the independent data monitoring committee has been giving us the green light every time they met. We have a we have another question here in the room. Go ahead. Thank you. Just two questions from me. 1, maybe starting with Doctor. Merit, since you're a part of the FLORIDA 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 1690? And then the second question would be for Pete and Will lead. You had a chart up of the pathway of rebalancing the inflammatory different ways of rebalancing inflammatory, I guess, phenotype of different cells within the body. I'm just curious, you had one point up there, first, Finco seen 1 phosphate receptor as a target. And we know you're also interested in repolarization of different immuno, inflammatory cells like macrophages. I'm just curious, like, 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 like sequestering lymphocytes. That was a lot, sorry. So I'll just give my very quick view. I, you're asking me an almost impossible question. Certainly the drug was very well tolerated when we used it in the trial. One of the challenges of IPS studies is that they don't have a measure of individual response. FBC is very good for showing population change. But unlike cancer where you might expect to see tumor regression with a successful treatment in IPF's success is stability. And because of the variability of the disease, we will see in some patient stability And I don't know if that's treatment success or just that patient's disease. So I don't think I can honestly answer you except to say it was well tolerated. And then the broader question on our approaches. If you look to the tolling of the record, that's where the interest come from. So we see, 3 polarization across cell types. So does every cell type react as quickly? No. But if you see across the immune cells, you see it across all cell types, some are a bit more sensitive and some are less less sensitive. So 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. So and that's we're still there between our old mode of work. We select the target. We observe we see good UV activity and we start to run. So coming years, we'll get much more refined on that and then select early 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. So that is the plan we are moving towards, but if you look to the current programs, effect, it's a little bit closer to that. That's what I can say, what we see. Okay. We have time for just a few more questions. And I'm going to go back to the phone and see if there's any question, one more chance. Thank you. We take our question from James Quigley of JPMorgan. Please go ahead. Thank you for taking my question. On the filgotinib program, so the osteoarthritis and ankylosing included by devices, trials. Given the black box warning for RINBLOC and the comments from the FDA around the class effect, has this changed any of the, the recruitment or the feedback from investigators or monitoring required in the trial? Thanks. Thank you for the question. So, the quick answer is no. I think the probiotic events have been, essentially well known for some time in this space and in all of our 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 holes even more rare. But no, we have not been having any difficulties or any concerns from firm investigators that I'm aware of around this and they're quite familiar with that. Okay. A question from Greg. Great. Thank you. And thanks. Great presentation this morning. I've got three questions. Maybe the first 2 are for Pete and one for Waleed. On the Toledo program is very interested by, the approaches of having a Toledo PAM and a toll 2, toll 3 and a toll selective molecule, can you maybe walk us through what the incremental advantage would be of just going toll free selective versus toll 2 and toll 3. So is there something about toll 2 that might be potentially, I don't want to say problematic but what is it about going after total 3 selective that might be a better approach? And then I was very interested about your interest in going into the SINR RNA space and was wondering where the opportunities you see are in going after that mechanism, are there is there something incremental that can be improved upon, from the SI RNA technology perspective or is it just an opportunity for the company to go into different diseases and targets? And then for will lead just in terms of just coming back from ACR, we'd 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 cadacitinib in terms of, the lunch trajectory, what they're thinking about their, excitement or not about that product? Thanks. Akiko, first. So the total program Well, there are 3 targets. We learn as we go. And from the way I've been teach, I would by nature, go from a selective. Instead that every day I see my scientists and they have designed to novel selective, It's not easy to be that Pentolado, let's be clear. So it's more than this one. Targets, 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 like that. Each have their property, their strength, and we learn as we go toll 3 indeed, if we look to the profile, it is from a scientific point of view, the least interesting because it does what an entity inevitable currently, I bid more, but there are other mechanism of action with similar profiles. On the other hand, if I can take the last patients off and I'll leave him up, I'll be happy to do that as well because if an oral does the same, we'll do that as well. So in that sense, the kind of a low base case, scientifically, If I can do take that last patient of injection, I will do that. So no problem there that if we can play that game finally, we will do that as well. So let's be clear. But I hope scientifically and for patients long term treatment is more in those others where we restore the balance in a better way. So let's be clear. Two aspects. 1, it's really a logic next step if you look to the platform. That's why we want to do it and we believe will become much more efficient in selecting solar resets, even models because for every target, because it's always a long walk in a dark in the dark honesty to find them. And it's always the question is the compound good enough or is the model good enough. So we really spend a quite a lot of time iterate, just making better compounds, other things, why even as IRNA fee could, we would get good at that. Normally, you should do that easier. Honestly, the limitations is how do we get into the tissue. And so it's quite think we'll know that for delivery, there is no problem to get those into delivery. So, and we are interested in Nashville for Nation. This would be an obvious choice. In HBV, I've been impressed. I must say a bit what those compound does is a single injection every month gives you a nice fire load drop within once a month injection. Okay. This is becoming competitive. I would say, I worked in that area at the early days and the feet done nicely. So it's clear that tissue by tissue to organ by organ, you will either need to rely on the Fischem properties or do a targeting trick to get it there because it might serve, they are going to be limited in terms of the delivery. It was a question for you? Yes. So I mean, I think what I can say coming back from ACR, it's really a good time now for JAKs I think there's the attention on the JAKs and the amount of publications. Of course, the launch of Oopa carries a lot of sound bites to speak and presence in the meeting. But I think also over time, people are getting or the physicians are getting much more comfortable with the Jack of the 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 over time and some of the biologics. Also the safety profile, people are getting more, aware and I don't know if you can stay comfortable with it, but at least they're familiar with it. I guess, this is the word that I'm looking for. And I would say that anything that's good for the Jack Glass 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. So we're very excited to forward for next year's ACR where we will be the center of attention because by that time, we should be approved already. And 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. We're going to wrap up for now. And I just really appreciate everyone coming in person here to the Westin and dialing in and listening in, to our webcast today. Are still burning. You can contact Sophie or myself. We'll try to get them answered for you today. And, again, I thank you, and I hope that you have a wonderful day today. Goodbye.

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