Thank you all for joining us today for our virtual R&D roundtable covering the Toledo program. I'm Elizabeth Goodwin, Investor Relations, also representing colleagues in our IR, R&D, and Communications teams who have worked hard to bring you this information today. This recorded Zoom webcast is accessible via the Galapagos website homepage and will be available for replay later on today. Sell-side analysts and professional investors are invited to pose questions at the end of our call. I'm going to give you a dial-in number now. That's 44 for the U.K., 207-192-8338. That's 442071928338, and the code is 3312849. I'll give that number again a little bit later.
There will be additional numbers visible on the webcast player screen when we come to that part of the event. Now moving on to our forward-looking statements. I would like to remind everyone that we will be making forward-looking statements during today's webcast. These forward-looking statements include remarks concerning future developments of the pipeline, the Toledo program in particular, our company, and possible changes in the industry and competitive environment. Because these forward-looking statements involve risks and uncertainties, Galapagos's actual results may differ materially from the results expressed or implied in these statements. Now I'd like to go over the agenda for today. Our program will last approximately 1.5 hours. First, we'll start with a talk. CEO Onno van de Stolpe will introduce our innovation approach. CSO Piet Wigerinck will talk about our innovation with the Toledo program.
CMO Walid Abi-Saab will discuss our clinical strategy. Onno will come back to wrap up. You'll see a PowerPoint presentation on screen during their talk. This will be followed by a Q&A session. You'll get more instructions at that point. That's all for our logistics today. Now it's time for us to get into what you've all really been waiting for. I'd now like to hand over to Onno to tell us more about the approach to innovation at Galapagos.
Thank you, Elizabeth. Very excited to finally take away the wraps around the Toledo targets and the Toledo story. We are going to highlight that today in this session. Thanks for joining this. It's a very positive session. We're all very excited about sharing this information with you. Innovation is really in the DNA of this company. We have been focused on innovating, and innovating since the start 22 years ago. We pushed the scientific boundaries. We are very much science-driven. Science is so crucial for anything we do in this company. We follow the biology along the way. We find a target, develop the drug, see what areas it can be best used for. The Toledo group is a very good one, where we're exploring various diseases that potentially could benefit from the Toledo drugs that we are in clinical trials with at the moment.
We're clearly very innovative. We are focusing on new methods there, always focus on new mode of actions. Our approach to innovation, as I said, is novel targets that we identify with our platform, combined with chemistry, always supported by biology, with technologies to very rapidly go into clinical trials to identify the target as the right target to treat various diseases. We have a very ambitious path in deliverables. Our objectives are to come up with six new targets per year, bring that to three to four preclinical candidates per year, three proof of concepts, that should lead to one phase III start every year. It's an ambitious program for a small biotech, and Galapagos still is, but we are delivering, and we are getting more and more programs into the clinic.
It all boils down to the target discovery platform that we started 22 years ago based on adenoviral technology. What we did is putting a small piece of human DNA into an adenovirus backbone that when it enters a cell, a human cell, it will actually stop one specific protein being produced in that cell. By doing that with over 6,000 different genes of the human genome, we can rapidly zoom into those genes in the human genome that are responsible for certain diseases. When we identify such a target, a hit, then we can develop a drug that ultimately will do similar to the adenovirus when it enters the cell, when it enters the human body, actually will regulate and stop the specific protein that's overproduced in that specific disease.
It's a very robust platform that has delivered many interesting targets so far, and the Toledo group is clearly one of them. If you can see here on the slide on the right is actually the Toledo protein. For those chemists and biologists, you can now identify the targets based on this graph. You can get to the next slide. Clearly, our innovative approach with Toledo is now coming into a stage where we are going to get results in patients. It has been a long way where we initially identified the targets and then got excited because of the dual mode of action. We confirmed that in animal models and also in human phase I healthy volunteer studies, and we are now launching a broad phase II program to see how this family of drugs behaves in various inflammatory and fibrotic diseases. Very exciting for us.
The question is: Can we make a difference? Of course, you never know until you're actually in the clinic in late-stage trials. It's always a tough decision in what diseases to go for, but the inflammatory diseases clearly are in need for new classes with better efficacy. If you look at psoriasis than 20 years ago, it now has much better drugs available for treatment where up to 90% of the patients react very favorably to treatment. However, in other inflammatory diseases, this improvement has not gone as fast as with psoriasis, and there's a clear unmet medical need, a need for better, safe, and effective treatment options. That is the difference that we would like to make in inflammatory diseases with the Toledo group.
You all know we have filgotinib on the market here in Europe and shortly in Japan, which is a very exciting drug as well. Clearly, we would like to go another step into treatment of these inflammatory diseases, and we hope to develop the Toledo group of molecules as a next generation in treatment of inflammatory diseases. We can get the next slide. It's my pleasure to hand it over to my CSO, Piet Wigerinck, to give you the background on the Toledo program before we will actually continue with Walid on our path to patient data. Piet, the floor is yours.
Thank you, Onno. We promised to raise the curtain on our Toledo program today, and we plan to do much more. I hope that by the end of this presentation, you will share with me our enthusiasm around this novel mechanism of action. We call it a master switch. This is new because Toledo acts in a novel way. It acts in a way which is different compared to current drugs. The novelty is that it has a dual action. It blocks on the one hand, the damage and stimulates the repair. That's what I want you to remember at the end. Our body can only work because it's full of systems that act and control. There is always a balance. That's also true in immune system.
We need cytokines, and they are colored here as the orange ones, that act when we get an infection, when a virus infects us or a bacteria. This is the first phase of the fight. When they have done the job, we come into a second phase, and then we need the green ones. These are anti-inflammatory cytokines and players, and they take care of the healing. When there is an infection, we always have a fighting phase and a healing phase. It's important that those two are well-balanced because in patients, what do we see? The fighting phase, that's going well. The healing phase is not there because the balance is lost and as a consequence, our cytokines, our cells are going to damage the body. They will cause ulcers, damage, it will harm bones. Current therapies all are based on the same principle.
They try to damage the excess of the pro-inflammatory cytokine. They take away that excess to restore more or less the balance to avoid that the healing can take place. They're going to take away and make sure that the small amounts of the anti-inflammatories can do the job and can limit damage. With Toledo, we have different ambition, and we've seen those data, and I'll share them with you. We want to play or we play with Toledo at both ends of this balance. We, on the one hand side, limit the damage by decreasing the number of pro-inflammatory cytokine and cells, but at the same moment, we increase the anti-inflammatory cytokines and cells. That's what I'm going to show to you today, and that's why we're so enthusiastic about this class. How do we find these novel existing targets?
Well, those amongst you who follow us for a long time know it's a long way, and it all starts with a diseases . On the left, you see here a cartoon of the gut. Talking about the gut is always fun because while the gut is not the inside of the body, it's, in fact, the outside of the body, and to protect the body, we need a layer. These are these green cells, tightly connected epithelial barrier cells. You also see there a purple star-like cell, which spikes through the barriers. This, in fact, is a dendritic cell, and they act as sensors. They're extremely smart sensors because when a bacteria passes which does not cause harm, they don't act. When a noxious bacteria passes, they will give an alarm signal, and then the whole immune system is activated and recruited.
Rather than setting up different models, one for the epithelial layer, one for the dendritic cells, one for the macrophages, we decided to go for a more complex model and make our iBTS, which was a bilayer model. In fact, on top we have the barrier where we can measure whether it's really very sticky and nothing leaks through, and below we put down those sensor cells, the dendritic cells. In fact, this is an extremely cool model because if you will add Lactobacillus, which is part of yogurt, our barrier becomes stronger. While on the other hand, if we add a dangerous bacterium like E. coli, the barrier get lost. Really a model which in terms of relevance and the complexity we had seen before.
This model allows now to us to knock out targets in the immune cells and measure the impact of knocking out the target in the immune system on the epithelial barrier. It is by screening this type of models and assays that we discovered the Toledo. Early on, we were intrigued, and we were lucky that we could find a non-selective tool compound, but as well with that non-selective tool compound early on, we could prove that in fact the barrier was maintained. We could put in as much cells bacteria as we want. If we compensated with compounds, if you blocked that target, the barrier stayed intact. We started to measure all of the cytokines in these models, and we saw that many were going down. Also, our surprise, a few were going up, and this was something we had never seen before.
We wanted to confirm that. We then set up a macrophage assay where in fact indeed we could confirm in the second type of immune cells that with an increase of dose, we saw a decrease of the pro-inflammatory cytokines and an increase of IL-10, which is a prototype of the anti-inflammatory cytokines. It was the first time that we say, "Wow, this is cool. I don't think anybody ever got this." This target really, this is something special. Now I'm jumping five, six years to first give you a bit of the breadth. We've optimized compounds. We then started to look broadly in all types of immune cells. To our surprise, in fact, you can see on the left, you see there the macrophages, the monocytes. You see a decrease of TNF-α, a decrease of IL-12, a decrease of IL-1β .
As in our model, we see an increase of IL-10. When we go to the dendritic cells, we see a similar picture to different cytokines. TNF-α going down, IL-12 going down, IL-23 going down, IL-10 going up. All of the drugs that we currently have, in fact, they react as well to the Toledo, and on top we increase IL-10. In T-cells, we see a decrease of IL-2 and interferon gamma on, and in B-cells on the right, we see again a decrease of TNF-α and increase of IL-10. This is a switch, a master switch, which in many cells of the immune system has a similar action. It really does something which we had never seen before. That's why we call this our master switch in immune system.
I'm not going to keep you waiting until the end of the presentation to reveal the target, and we're going to do that now. We call it TOL1, TOL2, TOL3, but behind that code, in fact, and many of you guessed that right, are the SIK1, SIK2 and SIK3. These are named salt-inducible kinases. What has salt to do with the story? In fact, extremely little. The first member of the family, SIK1, was discovered in 1999 when animals were fed a high salt diet, and then one of the enzymes that they showed that was popping up was SIK1. For SIK2 and SIK3, there is no link at all with salt. Salt-induced kinase is the name, but is of zero link to our story. We are working on three pre-selected candidates currently.
You can see GLPG3970. That is the focus of today. I will only show data of 3970 because that's a component moving to patients, blocks both SIK2 and SIK3. GLPG4605 has a similar profile and I will not discuss today. GLPG4999 is a bit of a strange compound. It's selected on SIK3 only. It has a bit of a different profile that's also for a later discussion. Will not be discussed further today. Next slide.
Yeah, it's good.
Alan, you have the movie now? Yeah. How does SIKs work? As you can see there in the movie, you see the yellow strings and green strings. In fact, these are the mRNAs coding for the anti-inflammatory and the pro-inflammatory cytokines. In immune cell at rest, they are in balance. This whole system, in fact, is under control of SIK, and SIK controls on the left, the HDACs and the CRTCs. Give me a minute here. HDACs, in fact, they are blocking NF-κB, so if they reach the nucleus where you see the DNA strength of the NF-κB program, they will block that. CRTCs, they have the opposite function. If they can get to the cell, they will activate the CREB system.
SIK is a kinase, so it adds a phosphate group to both the HDACs and the CRTC. Both stay out of the nucleus, and they don't work. There is a basal functioning of NF-κB and CRTC. This gives us a kind of balance. Next slide now. When there is an inflammatory trigger, what happens now is that this whole SIK system is biased. There is a direct activation of NF-κB, and you will see a vast increase on the left from the pro-inflammatory cytokines. What happens now if you switch off this master switch SIK with Toledo next slide? You get two opposite functions. The SIK is blocked. It's not phosphorylating anymore. HDACs and CRTC.
HDACs go to the nucleus and they block NF-κB. You have a vast decrease of pro-inflammatory cytokines, while CRTCs also go to the nucleus. They activate the CREB system, and you see an increase of anti-inflammatory cytokines. This is why this mechanism is so unique, that with a single switch of the button, you're going to completely invert what is normally happening during an inflammatory process. You play at both ends. You invert completely the picture. That is the heart of the matter, how SIK works. Next. Now we go back to the presentation. Next slide. We discovered this target quite a while ago. It was around 2012. We will later add to the presentation a number of external references. You will see the first appear as well in 2012.
With those novel mechanisms of action as Europe pioneers, in fact, the work is going slow because we don't have any tools to confirm. It took us a while. In 2014, we set up an HTS screening. As soon as we had first hits, in fact, our chemistry team starts to work. From 2017 onwards, we've been making preclinical candidates. Up- to- date we have four. We plan to do much more and even increase the speed over the coming months. We have those three members, SIK1, SIK2, SIK3. In fact, we want to combine all of them over the coming months. Right. We have in fact set up for our company a massive effort. We've dedicated the largest chemistry team ever. We've dedicated the largest team to understand this mechanism of action ever. We've synthesized a couple of thousand molecules.
We initiated our chemistry work on more than 10 different series, and we're really chasing every selectivity profile that we can think of. We've been filing patents and more to go. Currently, about one-fourth of the company, directly or indirectly in research, works on this program, and we really want to push this to the max. You can see on the right we have the different profiles. My ambition is, in a couple of years, we'll have plenty of compounds with different profiles blocking SIK selectively, one only, duels, and triples there. Next slide, please. Just to give you an example on how the chemistry worked and what the chemistry did, on the left you see the typical output of the screen.
Those orange dots, where only a few actives are sitting in the left corner there, meaning they have low potency and they are not selective because they have the same distance to any axis. On the right, you see how with this chemistry effort, we have grown our series, both in terms of potencies and in terms of selectivities. We have selective SIK3 duals. We work on selective SIK2 series. We work on selective SIK1 series. This will be a maintained effort, and we will come with whatever profile we believe is sufficiently interesting to be put in patients. Next slide. Let's now go back to our IBD model.
This is a cartoon of an inflamed colon, and you can see by the fact that the bacteria, the green dots that are sitting in the lumen as well, they pass a bit through our barrier, which at the moment is leaky. The dendritic cells, they sense the presence, and they activate the whole immune system. They're going to activate the macrophages, the neutrophils, and also they will recruit the T-cells, TH1, TH2, TH17, and all of them will produce many cytokines to form and to attack those bacteria. What you see as well on the cartoon, there's only one or a few amounts of T-regs. What happens now when we block with the Toledo, we're going to block both dendritic cells, the macrophages, and you will see the balance turn. You suddenly see a large amount of T-regs.
We see suddenly the green cytokines appearing, and we don't see any of the pro-inflammatory cytokines anymore. With the Toledo, you can locally distort, completely reverse that interplay, and the barrier will restore, and integrity will be restored as well. Bacteria from now on will stay in the gut. Let's now go to some in vivo data. Today, we only show data of 3970. The pictures might look very similar to what I've shown before, but that was with different compounds. Today, all data are around 3970. These are three IBD models, and the uniqueness of the Toledo family, in fact, that these compounds work in all three models. We've seen good activity with JAK inhibitors or other mechanisms of actions in one of two of those models. Never in the three models at the same moment.
On the left, you have the DSS, and that's in fact a barrier model. In this model, with a chemical, you will damage the barrier integrity, and you see how quickly a compound can restore that barrier integrity. 3970 scores as much as our internal positive control. In the middle, you have the T-cell transfer model, and in fact, that is more a balance model because you may take healthy animals, you're going to infuse a mix of activated T-cells, you distort the balance, and as a consequence, you get all of the damage on the colon. Positive reference is a T-cell blocker, abatacept here. Again, you see that 3970 is doing nicely the job to block the damage in the T-cell transfer model. On the right, the MDR1 model is less used, but it's quite close to the disease.
In fact, it's a model where you have sensitive animals. You will trigger them with a bacterium, and their colon will get inflamed. Even more, the IL-17 antibodies in this model worsen the disease like they do in the clinic, while IL-23 antibodies will work. It's a quite relevant model, and also in this model, 3970 has shown mild activity. Next model. Now we'll dive a bit deeper into what we've seen in the T-cell transfer model in the tissue. Now I'm going to show you really experimental data, and let's start with the macrophages here. What you see here on the left are the activated, the pro-inflammatory M1 macrophages, and upon treatment, you see the number going down.
Same model on the right, what you see here is the M2 macrophages, the healing ones, when we induce the disease, their amount is quite low. By turning a switch here, we turn the program, and the M2s will increase. We really have quantitative proof that we play at both ends of the balance here. Next slide. We've also measured locally the cytokines. These are now measurements in the colon tissue after treatment. On the left, you see the TNF levels. We start with the healthy animals unchanged. We're going to challenge them with T-cell mix, and you see an increase of TNF in the colon tissue. This is colon tissue. I will stress that. When you treat the animals with Toledo, and you see a return to almost the healthy levels of before of TNF-α. A very strong blockage of the pro-inflammatory cytokines.
In the middle, the same, the opposite story for IL-10. IL-10 is the cytokine that's going to induce the healing in the disease state. These levels decrease. They are low. We apply Toledo, again, we see an increase to almost normal. You really play with all of these data I show you, we play at both ends of the balance. Take TNF-α and IL-10 were only the prototypes of a much broader panel. On the right, you see at the top, total panel of the pro-inflammatory cytokines we measured upon treatment, they all decrease. Below, you see two members of the family of the anti-inflammatory cytokines, again, upon treatment, both members increase. We see across cell types, across cytokines, a system picture, we play at both ends of the balance. Toledo works on multiple immune cells, is also active in multiple disease models.
We've tested, I've shown you the models of IBD. I will show you data for psoriasis, psoriatic arthritis, RA. We've tested lupus models. We've tested OA models. It's not everywhere active. Like you can see, OA, we don't see activity with our compounds. Show you the most important one on next slide first. Next to the anti-inflammatory models, we next in the second phase as well start to be interested in the fibrosis models and also there, 3970 shows nice activity in two models of fibrosis. I'll show you the data. Again, we'll concentrate today on explaining the switch, how these molecules work in a fibrotic setting. I promise you to take it as well at a next occasion. Next slide. Data on psoriasis. This is in fact a local model. We are going to inject IL-23 in the ear, and there's a very easy measurement.
You just measure how much the ear is swelling, and you can prove then that your compound has an anti-inflammatory activity. You can see that here, 3970 scores as good as our positive control in this model after oral dosing. It's oral dosing compound is penetrated to your body, go into the skin, and locally does its activity there, and clearly it shows an activity as good as a positive control, which was a JAK2 inhibitor, I think. Next. Okay, now two models of arthritis. In effect, on the left, we have the CIA, on the right, psoriatic arthritis model, and in fact, two quite different models, although it's both bone and joints. The CIA model is a model where disease is driven by B and T-cells, while the psoriatic arthritis model is driven by other cells.
As I showed at the beginning, Toledo shows an activity in T, B-cells, macrophages, and dendritic cells. CIA is clearly a check that promise of B and T-cells that are coming through. You can say over here that 3970 score as good as Enbrel in this model. This is a harsh setting. We wait long before we start to dose so that there is good disease. It's a therapeutic setting, as we call it. We start to dose, and we see effective decrease of the disease with these compounds. The psoriatic arthritis model is a bit of a different model. There, now we inject IL-23, let's say, in a systemic mode, and you get an inflammatory response on the bones and certain of the tendons associated with the bones, typical for the disease as well.
Again, there, this is becoming a repetitive story, 3970 scores as good as our positive control. Finally, in terms of animal models, I told that we have shown activity in two fibrosis models. On the left, you see the bleomycin. The model is what it is. The windows are small, 3970 here was even better than nintedanib, which is a positive control. Clearly an indication that there is an anti-fibrotic activity ongoing here. There's a good rationale here, as I said, I'll keep that for a next session. On the right, a chronic graft versus host model, where as well you can see that the Toledo mice scores and even better scores than nintedanib. Next to the autoimmune, which is our start of the program, we as well plan a later wave of fibrotic indications, Walid will tell you more around it.
What do we have today ongoing? We have GLPG3970, SIK2 and 3, starting phase II. We start to those patients. Walid will explain the breadth and the thinking behind the program. GLPG4999 and SIK3 selective, we are IND ready. We wait for approval, and we will start phase I. GLPG4605 is a very specific SIK2/3 compound. Explain as well later. It's kind of a backup, which has different properties compared to GLPG3970. Behind these three compounds, we plan to keep on, as I said before, looking selective SIK1s, SIK2s, SIK3s, and then SIK1 combined with 2 and 3. Whatever we can, when we find compounds that show an interesting profile, different of what's out there in the clinic, we will push it forward. We've put GLPG3970 in preclinical testing, and from there we go to the clinic.
We've performed a phase I single ascending dose, multiple ascending dose, and in fact, the compounds in terms of PK performed excellently. It's a once a day compound. Absorption is fast. We see dose proportional exposure. Based on the half-life, once a day dosing really is our default here. As well what we see with the compound, the chance that we'll have drug interaction problems or issues later is quite low. In terms of exposure and dosing, this is an easy compound to move forward. The more interesting compounds or data came in effect from the PD effects that we've been measuring in this phase I. You will see now graphs on the left on the TNF-α levels, day one on the left, day 14 on the right, and then IL-10 as well left day one, right day 14.
What we do here is we take blood samples out of those healthy volunteers at specific time points. We're going to trigger the whole blood and then measure whether TNF-α is there or not in IL-10. As you can see, orange is placebo. We don't see any effect on either TNF-α or IL-10. The low dose effect already gave an effect in TNF-α, not yet or very little on IL-10. From the second dose effect onwards, we will clearly see robust decrease of the pro-inflammatory cytokines and a nice increase as well of the anti-inflammatory cytokines. In terms of safety, I can be very short. It's all a quite boring phase I study, so we've seen what you typically see, and we've seen nothing special. All lights on green to move forward into the clinic. With that, I want to give the word to Walid.
Thank you, Piet. Good morning, good afternoon, everybody. I hope you can hear me well. I hope we got you very excited about what we've seen so far with this program, I'm really excited to walk you through the clinical story and our approach there. Can I have the next slide, please? This is a slide that you've seen before, as we've been talking about, the foundation of what we do and what guides us at Galapagos is science. When we set out to figure out how we want to approach this platform and how we want to learn from it, we looked at the broad application that we have in inflammation.
As you can see here, between innate immunity, innate and adaptive immunity, you can see on the left-hand side, these indications that are more close to innate, like psoriasis, UC, and CD in IBD space. On the right-hand side, you have rheumatoid arthritis, lupus, Sjögren. In the middle, getting from both worlds, you have psoriatic arthritis. To a great extent, that colors the way we're going to go forward. At the same time, we were taking a broad approach so that we can learn from the lead compounds so that the follow-on compounds could be better positioned and potentially could move faster so that we can make these promising SIK inhibitors available to the patients as soon as possible. If I can have the next slide.
The first step here, and that's the first orange wave, so to speak, the first wave, is to cast a wide net in looking at a number of diseases across the innate and adaptive immunity space and in a series of signal detection studies to understand the biology, link that to what we've seen in the phase I effects, as well as in animal studies. The next wave will be to essentially go further in those areas where we have a clear effect in these signal detection studies and go into dose range-finding study, but as well expand into other indications. For example, if you start with ulcerative colitis in the first wave, you can go into Crohn's disease. If you start with psoriatic arthritis, you can go with ankylosing spondylitis, and so on and so forth. Sorry, staying at the same slide.
Then you have that third phase where you can further develop and go into confirmatory program for the studies, the indications where we have effects in the dose range-finding study, but also initiate our fibrosis platform as Piet described below. Now let's dig a little bit in more details. I can have the next slide, please. To validate this initial space, we started with a psoriasis study. Psoriasis is not really an indication that we plan to continue developing based on the way we think right now. The reason why we started with it is because it lends itself to very quickly be evaluated and generate clinical data for us to indicate where we need to go next.
Because we can do this in a phase I setting, because most patients are relatively healthy, with the exception of some, the skin manifestation of their psoriasis. If I can have the next click, please. You can see we're going to be casting a wide net across that platform that we talked about, looking at signal detection studies in ulcerative colitis and rheumatoid arthritis as well. Later, which is going to be starting later next year, I'll show you on subsequent slides, we're going to be expanding into more challenging indication, but also very interesting to understand the biology, lupus and Sjögren's syndrome. Next. You will have a set of studies, where we can go and do dose range-finding studies in RA and UC. For psoriatic arthritis, I'll talk to you a little bit more further on.
That's an indication that we're actually trying to accelerate faster because it promises to make these potential therapeutic agents available to patients as quickly as possible. When we do go into indication expansion, you can see the adjacent indications that I talked about, Crohn's, ankylosing spondylitis, but there are also some others. That's why we didn't label that last one. There could be others that we will find out more and learn more along the way and be informed by that first wave of signal detection. Lastly, you have that phase III, where you can go into confirmatory studies for inflammatory diseases, but also start exploring the fibrosis indications and other chronic indications that we're going to go after. Next slide.
This digs a little bit deeper on the timeline and gives you a sense of the parallel set of signal detection proof of concept studies, starting with the psoriasis study, which is again, an additional cohort in our phase I. The ulcerative colitis and rheumatoid arthritis are two studies. I'll talk about them in subsequent slides. Later we're going to come out with lupus and Sjögren's in beginning of 2021. Three of those studies are already active and recruiting, and the other two will be coming up shortly by the end of this year, early next year. We have five different proof of concepts to investigate a broad mechanism action to be able to get a good sense of the overall biology and casting a wide net and learning from it.
We expect to have top line from these studies as of the middle of 2021. There's a caveat there, is that COVID is a bit uncertain. We're hoping that we're going to be able to move according to the pace that we want to. There could be some difficulties that we would see along the way. In the case of psoriatic arthritis, if you remember, I have a picture on the top of the innate and adaptive immunity, and then psoriatic arthritis is there in the middle. Based on the number of studies that we've done pre-clinically, and that Piet have gone through some of them today, we believe very strongly that the biology support this indication, and we have a very good conviction that we have a good probability of success.
As a result, we decided to prioritize this, to take a bet, a bigger bet on this. Instead of waiting until we do things very sequentially, we plan to start immediately into dose range-finding study in psoriatic arthritis in the middle of next year. Then with that, move as fast as possible into phase III with the expectation that if our bet is correct, we will make available these potential medicines to the patients in about a year and a half to two years earlier than otherwise. Now let me take some time to walk you through a bit of the design of these signal detection studies. You have the first one called CALOSOMA, which is the psoriasis study. As you will see across the board, those are small signal detection study.
In order for us to be able to cast a wide net and learn, we must do these as smaller studies so that we can get initial information and not spend a lot of money at risk, but at the same time, also not take a long time to get the results back. With that, also, you have to bear with us. When you experiment, there's potential for some studies to have better results than others. When we start talking to you about them next year, you guys should expect also that some of them will look very good, but maybe some maybe not as good. We need to be fully aware of it. We are going there with eyes wide open. This study is essentially, we're going to have 25 patients, 10 on placebo, and 15 on active.
These are typical patients with moderate to severe psoriasis, with have a baseline of at least 12 and above, and body surface area coverage of 10% or more. We will look at, of course, safety and tolerability as we often do, but also at efficacy in the usual PASI scores and so on and so forth to get a sense of the activity. In addition, with those trials, we always look at biomarkers and things of that sort as well. The next one is the SEA TURTLE study in ulcerative colitis. That study, again, is a similar design. Generally, it's a six-week duration, 10 on active and 20 on placebo. These are patients with moderate to severe UC, who have been exposed to treatment before, of course. The key outcome is the usual stuff that we look at, the endoscopy, biopsy.
We look at the Mayo score and the partial Mayo score. Of course, we will look at biopsies, and with those, we get a pharmacodynamic endpoint as well to link back to the clinic, link back to the healthy subjects, and learn from this. Last of the signal detection study is the LADYBUG study, which is a study in rheumatoid arthritis. Again, it's a study of 15 patients on active and 10 placebo. It's a bit reminiscent of our first study that we've done a long time ago in Moldova with filgotinib, and we're hoping that we're equally going to get some fantastic data with that study that will get us excited about going forward there with this one. These are, again, patients who are methotrexate IR.
They have moderate to severe active RA. We usually look at the usual symptoms of RA that you know very well. I hope, I can go to the next slide, that I was able to communicate to you that the approach that we have taken in this program is an ambitious but also an informed development strategy. Where we take first the fastest way that we can get clinical data in a psoriasis study in the phase I-A/B setting so that we can quickly get that information. We also can take a bet on psoriatic arthritis based on our belief in the biology and also on the data that we have accumulated so far, particularly the pharmacodynamic endpoint from the phase I study. That could make the drug available to the patients potentially up to two years earlier.
The learning approach that we take by taking the lead compound and linking back to the biology and translating back to the lab and also to the healthy subjects and have cross-learnings, will help us to position these follow-on molecule. Giving you an example. A follow-on molecule comes in, and based on preclinical data, we expect it to work in such, let's say, in RA. The pharmacodynamic profile that we get in phase I looks very much like what we expected to see in compounds that would work in RA, and it would be different than our SIK2/3. We can quickly go into a dose range finding study and not have to do a proof of concept study. Again, sort of speed development, but not only that, also position for the right indication. This is the approach that we're taking.
With every study that we do, our knowledge is going to grow, and ultimately, we will really unleash the potential of this brand-new pharmacology and what it could offer to patients. Lastly, we're going there with eyes wide open. We know that this program is early. We are monitoring everything very carefully. We've been monitoring, for example, safety, and we look at the biology of this from the beginning. We have a large group dedicated to monitor safety across all the trials so that we can detect signals very, very early and so on and so forth. We understand the promise of the novel pharmacology, but we also understand the potential unknowns, and we have all the systems in place to be able to deal with this and solve any issues, or if they were to happen, very early on.
I want to tell you that we are going there with eyes wide open, knowing full well about the exciting parts, but also knowing full well that there are certain things that are not known because of the novel pharmacology, and we are going to be watching this very carefully. With that, I will turn over to Onno to wrap up this very exciting story today.
Thank you, Walid, and thank you, Piet. I hope you all share our excitement with this program. Clearly, we are extremely excited and optimistic regarding Toledo. It is short in its development still. It's early days, but all the data, they point into the right direction. I think it's really the totality of the Toledo data that makes a difference here. It convinced us very much. It started with the identification of the target with a very complex assay. We saw in the literature that the mechanism made perfectly sense to focus on this one for inflammatory diseases. We got the preclinical data in, as Piet has shown to you, where time after time we saw very good and robust efficacy, something we have never, ever seen with a molecule before.
Lately, the phase I data, where we saw luckily very good data in healthy volunteers, but we saw also a proof of principle with the fact that we could see a dose-related effect on IL-10 and TNF. Altogether, we believe that we have a very strong package here that warrants hefty investment in further steps towards the patient. If we go to the next slide. It's clear that we potentially have a real master switch for inflammation different from anything anybody has shown so far, much broader in its application and hopefully much more effective than anything that is out there at the moment. We have, of course, with all the work that we have done over the past couple of years, a very broad and strong IP protection, intellectual property protection with the patents.
We have confirmation of the mode of action in the phase I that we did with GLPG3970 with a very good safety package. That gives us a lot of confidence that we have a right window to go into the clinic and into the patient trials. As Walid has just outlined, we are going into a very smart path in clinical development, which should accelerate to bring this drug to the patient, and hopefully shorten the development time substantially so that we can reach the market much earlier than the other programs that we have been working on. All this, you could question why we have kept this under the wraps so long with Toledo as a code name. It's all to not make the competition wiser than needed.
Clearly, we have a massive head start on the competition being in phase II, where as far as we know, no other molecules for inflammation have been in the clinic based on this set of targets, on the SIK targets. That competition lead will help us to secure an important market share whenever this actually would get to the market. A new class that potentially could change the way inflammatory disease and fibrotic diseases are being treated. What can you expect on the news flow? This year, we were very pleased that 3970 finished phase I so successfully. We're starting the proof of concept studies, the first one on the way, the second recruiting. That's all going in the right direction. Very proud on the teams that worked on this, especially in view of the whole COVID situation, that we didn't get delays here.
We're starting the next phase I for GLPG4399, of which data will come, of course, in 2021. In bold, you see in 2021 the readouts, which are, of course, very important of the proof-of-concept studies. Three proof-of-concept studies will read out in 2021, and the rest will read out in 2022. Will be a lot of data that hopefully confirm what we are expecting. You see a lot of other stuff happening. Phase I starts, phase I readouts. Look in 2022, where at the moment we are planning the first phase III, which would be a fantastic result if we achieve that. We have really accelerated the speed of this program with a couple of years. It's all possible now for Galapagos to do this, whereas in the past, we were always dependent on partners to finance the road forward.
As you know, with the cash that we received through the Gilead transaction, we can make our own development plan, move forward as fast as possible, and decide on the progression of these programs by ourselves, which clearly helps to speed up the programs. I truly believe that this is a once in a lifetime opportunity for Galapagos. Something all these people that work on this within Galapagos think is the project of their life. It is something so new, so promising, that this can change the way these diseases are being treated, and that that is happening at Galapagos makes us extremely excited and extremely proud. Of course, we still need to deliver on it, and it's a risky program because it's early, but all the signals are bright green, and we are looking forward to sharing more information as we go along the way.
With that, we would like to end the formal part of the presentation. I hand it over to Elizabeth for the Q&A. Thank you.
Thank you to our speakers. That concludes the presentation portion of the video webcast. We do invite sell-side analysts and professional investors to pose questions. I'm going to give you the dial-in number again. That's 44 for the U.K., 2071928338, and the code is 331289. There's some additional numbers also listed in the webcast player interface. You should be able to access those. I ask that folks who dial in to please mute your PC while you're speaking on the telephone. Otherwise, we're going to have some terrible feedback there. Folks who are interested in posing a question, you press star one on your telephone and then you'll come into the queue. Give folks just a moment to do that. Star one on your telephone. The first speaker is Brian Abrahams from RBC Capital Markets. Go ahead, Brian.
Hi. Thanks very much for taking my questions and congratulations on all the innovative work that you guys are doing. Two questions from me. My first is, I'm curious, as you sort of look at this mechanism, I'm sort of curious what shapes the differences in how you guys are planning to target different compounds towards different indications. I noticed that both GLPG3970 and GLPG4605 are SIK2/3 selective, yet they seem to have different profiles in terms of what diseases they work best in the preclinical models. I'm wondering if you could talk about what might explain that mechanistically and what guides your decision on targeting each compound. I had a follow-up question.
Okay. You can hear me now? Yeah. Thank you, Brian. You guessed the target well many months ago, so congrats on that. 3970 and 4605 are two completely different chemical scaffolds, and they behave completely different in the body as well. That's probably what's going to guide 4605 to a couple of specific diseases, because we see a disposition of that compound in higher amounts in certain tissues only, while 3970 is a compound that scores everywhere. With 4605, it's correct. It's the same SIK2, SIK3 profile. The behavior in the body is quite different. That's due to the chemical scaffolds. Thanks.
Got it. That is really helpful. Then maybe a question if you.
Oh, did we lose Brian?
Apologies, Brian. We've lost Brian. Brian, if you can just dial back in, we'll come back to you. I'm so sorry. The next speaker is Phil Nadeau from Cowen and Company. Go ahead, Phil. The line's open.
Good morning. Let me add my congratulations on your progress on this interesting target. I guess two questions from me. The first is that there's a suggestion of dysregulation in cancers. Have you completed your preclinical carcinogenicity studies, and what have they shown? Second kind of a technical question. Are all the compounds that you're developing kinase inhibitors, or are there other ways to regulate the activity, such as interfering with the AMP binding domain? Thanks.
Phil, thanks for the question. Like any drug that plays in autoimmunity, you need to be careful indeed, because you're working on balances where indeed, if you take away too much of pro-inflammatory cytokines, there is a risk for cancer. Those studies haven't started yet. We typically perform them later during phase III. From what we've currently seen in preclinical, it's not that we are heavily worried. Yeah, let's keep it to that. The second question, you want to know what all tricks we try to do to block the Toledos? Okay. We are open to novel modalities. We've explained last year at R&D Day that we will try ASOs and PROTACs. If we're successful with one of those, it should not be a surprise that this program is included. Thanks.
Great. Thank you.
Our next question comes from Evan Seigerman from Credit Suisse. Go ahead, Evan. Your line should be open now.
Thanks, Elizabeth, and thank you everyone for the great presentation today.
Go.
A few questions. One, can you hear me? Hello?
Yes.
Is that good?
Yes.
Okay, perfect. Sorry.
Yes, we hear you.
Looking at the psoriasis indication, there's been obviously with the PDE4 inhibitor with Otezla, but there's been a lot of interest in Bristol's TYK2. How do you think your asset compares to these other modalities? My second question is there any synergistic benefit in combining, say, 1690 with one of your SIK2/3 inhibitors in IPF?
Walid, you take the first question?
Yeah, let me take the first one and then toss it back to Piet for the second one. Our approach for psoriasis, and this will be seen in also other programs that we're developing, is to use them as a signal detection for us, and to better understand actually how the biology is comparing. We do not know. If you look at what is the unmet need now in psoriasis, I think we find the bar very high, and we're not necessarily thinking currently about developing our molecules in psoriasis afterwards. This is truly to teach us about the biology and then sort of complete our sort of taking multiple shots across the adaptive and innate immunity that we see in there. In our preclinical studies, as you saw from Piet's presentation, the data look very good. Now we'll wait to see what will happen in the clinic. Piet?
Yeah. Thank you. On the second question, does it make sense to combine the Toledos with 1690? Well, from a MOA point, they're completely different. In that sense, indeed, it makes clear sense to, at a certain moment, combine those. For our fibrosis franchise, we have an ambition to bring multiple drugs to the market and then come with an ideal combo pill at the end so that completely blocks the progression of diseases like IPF. From a mechanistic point of view, for sure, this makes sense. Thank you.
Great. Thanks so much. Appreciate it.
Okay. Our next question will be from Dane Leone from Raymond James. Go ahead, Dane.
Hi. Thank you for taking the questions, congrats on the progress with the Toledo program. Maybe I'll keep it to two questions on my end. Just going back through the timeline of the program, the original asset was GLPG3312, which was pan-SIK. It seems now that the program's avoiding SIK1 specifically. I'm just curious for your thoughts on, one, avoiding that target or potential issues running into hitting that target, maybe selectivity of these next-gen Toledo program assets over SIK1. Secondly, I was also interested in SIK2 as the backbone of these compounds and was curious to get your thoughts in terms of what's been described as maybe pleiotropic activity and expression within tumor cells, and how you think about some of these targets in relation to what's been understood within the field of oncology. Thank you.
The first question is on SIK1. If you looked carefully to the chemistry slide, you could see that we have families with selective SIK1. In that sense, I don't think the conclusion that we've given up on SIK1 is a correct one. I probably didn't tell, but when we screened, in fact, in multiple immune systems, if you check all our data, we've picked up every SIK member in one or another screen. I'm not going to say that we've picked all three up in the IBD co-culture, but we've picked up every SIK1 in one or another screen so that SIK1 has its place there, that is for sure. Whether you can drug it well and safely, that is a different question. We are not yet there, otherwise we would have that profile currently available.
For oncology, as I said, everybody playing or working in this field is aware. Are we heavily concerned? No. There are many publications pointing into many directions, and when we do the preclinical talks, we watch all of those tissues with special attention. There is nothing where we today say, "Guys, this is not moving forward." Thanks for the question.
All right. Our next question comes from Wimal Kapadia from Bernstein. Go ahead, Wimal.
Great. Thanks very much. Wimal Kapadia from Bernstein.
Go ahead.
Just firstly, coming back to Hi, can you hear me?
Yes.
Hello?
Yes.
Okay, great. Just coming back to an earlier question. When I'm thinking about the outlook for many of the diseases you are targeting, there are now multiple MOAs on the market, and the bar is really only increasing for future molecules. What really gives you confidence that Toledo surpasses that bar so that when the product does come to the market in several years' time, you actually will gain traction? Just tied to that, how would your plans change should some of the more advanced products in the clinic, such as bimekizumab, also demonstrate great outcomes in indications like psoriatic arthritis, given this was one of the reasons you just mentioned for not pursuing psoriasis? That's the first question.
My second question is just clearly very exciting in terms of trial outlook, but how should we think about the R&D spend trajectory tied to Toledo? Onno, you just mentioned hefty investment in your presentation. Any additional color on how R&D will be impacted and the trajectory moving forward would be great. Thank you.
Should I take the first?
Yeah.
We are guided by science and data. So far, our preclinical data suggests that this platform could make a big difference and actually be a paradigm changer. That's why we describe it the way we describe it. That's why we're so excited. That's why we've been investing a lot into it. We will see how the data look in the clinic, whether our story, which up until now, has been lining up very well when we take the next step to go into the various diseases, whether we see the same promising efficacy. In the end, we will base our decision on whether to progress or not on the magnitude of the effect, whether the chance we're going to be making a big difference in this space.
As you saw, there's a huge room in inflammatory diseases, whether they are in dermatology or PsA, but also in IBD, where there's a huge room for us to go up, like what happened in the psoriasis field 10, 20 years ago. Our hope is that we're going to be that profile. Now, of course, if the landscape changes with new medicines really lifting the bar, we just have to clear that bar. We have zero interest in developing molecules with minimal incremental change. This is something that we truly, fundamentally believe in at Galapagos. Again, we let the data guide us, that's how we will be. We're looking forward to see what we have, with that, adjust our way forward.
Well, with regard to the cost associated with it, clearly, this is a hefty investment. It has been a hefty investment for the last couple of years. However, if in the totality of what Galapagos is spending, these phase II trials are not going to break the bank. As you know, we are very well capitalized. We got the money from Gilead to invest in innovative new research, and this is clearly right in the sweet spot here. We believe that it's warranted to continue in this broad phase II trial.
We'll see. If the data justify going into multiple phase IIIs, we'll clearly do that. It will be likely in a combination with Gilead. Gilead has the right to this program after completion of phase II. They will have to opt in per molecule, and after that, costs are shared 50/50. It's up to them to join. They're extremely excited about this program, as you can imagine. I'm not concerned that the cost of this program will go out of control and make our P&L suffer too much. For now, we believe it's a very doable program financially.
Great. Thank you very much.
Okay. Thanks, Wimal. Our next question comes from Pietr Welford at Jefferies. Go ahead, Pietr.
Hi. Yes, thanks. Have a question, follow-up really on the first generation of compound or the first compound, GLPG3312. I wonder if you can give us some more details on why that was deprioritized and what it was that you saw, whether you think that is chemical specific. Perhaps you could then just follow up there. Could you tell us with regards to the, I think the 10 chemical series you said you developed. Are all of these four, GLPG3312, 3970, GLPG4399 and I think 4605, are they all different chemical series? Perhaps you could just put them for us in terms of chemistry in the various buckets that you've outlined to give us an idea of, I guess, how sort of you've covered that spectrum of drugs so far. Thank you.
Okay, let me start on the different chemical series. 4399, GLPG3312 and 3970 came from same family. That is small variation. The series coming behind, they are much more diverse. If you want to have a selective SIK2, I can tell you we've tried a number of series, so that is not an easy task. If you want a selective SIK1 as well, we've tried multiple series. There to get the selectivity right you need multiple series. The current, they are from a broader family. You can see the differences. Our specialists easily discriminate them. Broadly speaking, they come from the same family. On GLPG3312, so GLPG3312 was a pan-SIK compound, not that selective. We fooled ourselves a bit with early successes that if you targeted this to the colon, in the pre-cancer space, these are extremely easy and extremely successful.
We thought that as a proof of concept, if we can expose the colon only, it give our maximum chances of success to validate this target early on. Unfortunately, when we took it in the clinic, we hit one technical problem after the other, and then the program became so terribly slow that in fact GLPG3970 in terms of speed, took it over. We decided to progress faster program over all the slower because We could have done it faster with GLPG3312, but then the next would have taken again a couple of long rounds of optimization. In terms of speed, this was not going to be competitive and learning so much was a fortunate error we've made at the beginning. Thank you.
Okay, now our next question comes from Jason Gerberry from the Bank of America. Go ahead, Jason.
Thanks, Elizabeth. Thanks, guys.
Are you still with us, Jason?
Big picture in thinking of.
Yeah, go ahead.
Yeah, can you hear me?
Yes.
Can you hear me, Elizabeth?
Yes.
Oh, great.
Yes.
Yeah, just I guess big picture, some of the more high profile I&I markets where you're moving forward with Toledo, IBD, RA. Obviously, there's been a lot of success with oral therapies in the clinic. Is the idea broadly to sort of replicate the efficacy but achieve that without the systemic safety issues here with the Toledo program? As we think about the program modulating TNF and IL-10, can you talk a little bit about the dual action there, the potential for any offsetting effect if you dose Toledo too high? Just wondering if you can comment on some of the dosing considerations there. Thanks.
Maybe I can start.
Yeah.
I can get started there. I think if the mechanism of Toledo, as you play on both ends, should allow us to dose higher on the dose response curve in a safe way. In that sense, I have a bit of a different vision than the fear that I think I could pick up in your question. The fact that you play on both ends of that balance, in theory, you should be able of going higher on the dose response because you will not exhaust the system. In that sense, I believe that in terms of both efficacy and safety, there is room there to improve. Of course, if we end up with a profile which is similar to JAK and with a similar safety profile, this is not a success.
Because intrinsically, this has the problems of being much, much better than what is currently out there because we play out those both ends. Was there another question that I missed or?
No, that was it. Thank you.
Jason, can you repeat the question? The first one?
Yeah.
Okay. Thank you very much. Our next question comes from Emily Field from Barclays. Go ahead, Emily.
Hi. I just have a very, very high-level question. I know you touched on this in one of the previous answers. It would seem that part of the issue with GLPG3312 was a lack of selectivity. Thinking about this from a high level, would it be right to assume that as you progress to the next generations and iterations of Toledo, that would be of increasing selectivity? As you go about that, would you still plan to start with the broad indication set? As you move through the next generation of the compounds, would there be more selectivity also in terms of the relevant indications that you think that those potential assets might be relevant for? Sorry, very high level.
No, thank you. I will take the question on selectivities. Indeed, when I look to the presentation and the history of GLPG3312, you get the impression the way forward here to improve is easy. You just make more selective compounds. We're now doing the past six years of chemistry here, it has been a long and extremely interesting journey with a lot of surprises in that sense that as you have three players with similar or working around the same activity, it's full of surprises. I do not exclude that one day a combined SIK123 will be the better molecule. Especially early on when we look to the selective profiles of two and the threes. It is not such an easy picture as one might think, just improve your selectivity and you will get there.
The picture is quite complex, but anybody who wants to try is welcome, of course. It is a quite intriguing story and we learn every day. Thinking that only the selective profile of the future here, we are not there today. Walid, maybe you take on the indications that we want to take forward.
Yeah, sure. Thank you, Piet. Yeah, Emily, with regard to the indications, I think our ambition is that the lead compound is going to be generating a lot of information that we can then use to back translate and position the ones that are coming behind. Use essentially the, for lack of a better word, the pharmacodynamic fingerprint of each molecule to guide us in a given path based on which cytokines are changed and also based on the preclinical data. The first one is going to be casting a wide net. The others are going to be benefiting from that and actually going narrower in indications or maybe exploring other indications as well. It's hard to tell now before we have the data so that we can react to it. It will be data-driven. That's what it is.
Great. Thank you.
Okay. Thanks, Emily. Now we go to Matthew Harrison from Morgan Stanley. Go ahead, Matthew.
Great. Thanks, Elizabeth. Hello, everybody. I guess two things from me. First, maybe Piet, can you just talk a little bit about formulations here? I assume depending on which disease state you might be targeting, I don't know if you're looking at different formulations for these. Maybe if you could just walk through what you're doing in terms of formulation and bioavailability to different key tissue sets. Second thing, I know in the past when you've discussed this, you've talked about really wanting to have a significantly differentiated clinical bar. Could you maybe just comment on how you're thinking about that and what you think you'll be able to know from that perspective when you have some of these proof of concept studies?
I'll take the question on the formulation. Well, the formulation attempts we did was limited to GLPG3312 at the beginning. We had the idea, let's hit it hard in the core, and that failed. For the rest, 3970 is a relatively easy compound because it all was a solid and you have a fast absorption. In that sense, that was the best one, the formulation. I limited to GLPG3312, which is further past. We want to look forward. Walid, you take the second question on the indications.
Yeah. I think these are going to be small signal detection studies. Usually the way we do this, and this doesn't apply just for the Toledo program. For small signal detection, you can have three outcomes. One where there's nothing, and then you say, Okay, well, we went down the wrong path, and we need to go look somewhere else. You have data that really knocks the ball out of the park, and then you clearly see that you have very promising avenue, then you go and go fast in that direction. You have data where it shows you that you have a signal that's worthwhile further pushing in. Maybe you need to select your population better. Maybe you need to focus with the next study, looking at different endpoints to be able to tease that apart.
Our ambition is that. There's a lot of room. Let me take IBD, for example. Looking at these EBS remission rates that we talk about, and you have a difference from placebo anywhere between 10%-15% after 10 or 12 weeks induction. The bar is very low right now. We have huge room for improvement. Even when you look at maintenance, to look at steroid-free survival at the end of the trial of about 30% and 40%, and we're very excited about this because it's better than anything that has been seen so far. I like to see 90% steroid-free survival. I want none of the patients to remain on steroids longer term. There's a huge room for us to do much more.
These initial trials are going to send us toward that, but then we will have to confirm it with the larger trials. That is our ambition. Our ambition is to move the needle clearly, visibly, appreciably, clinically meaningfully, not just small incremental ones.
Okay. Thanks very much, Matthew. Our next question comes from Graig Suvannavejh from Goldman Sachs Group. Graig, go ahead.
Thanks, Elizabeth, and thanks team for the opportunity to ask questions. It's a great event. I've got two questions, if I could. The first one was just around the comments around safety. I believe the comment was we're seeing, or you're seeing what you typically see. I'm just wondering if you could just expand on what that means in your mind. Second, any initial discussions, and it might be premature right now, but any initial discussions with Gilead as to what their level of interest is in Toledo and how should we think about what their level of interest might be in light of what's happening with filgotinib and then the unfortunate disappointing readout for GLPG1972?
This one's safe . We had no volunteers dropping out. We had no events that caused any concern. There will always be somebody, be dizziness, whatever, but that is normal, and you always see one headache of some kind, and that will be what you saw. It was really an extremely boring phase I where we haven't seen anything which is specific to sorry, it's a bit difficult to talk about boring things. Onno, you take the question?
Well, in this case, boring is very good. Thanks for that phase I to be boring. Yeah, Gilead is clearly very excited about this. After the CRL with filgotinib in the U.S., they have expressed their commitment for inflammation long term, and they see this as the next big thing. Yeah, you don't have to worry about their interest to step on board when the time is there. It will take a while because they have the option after completion of the phase II studies. I'm sure they're eagerly following these developments, and we inform them on a regular basis, and they will be ready to act when the data are there. I fully expect them to join, and will share the phase III cost with us when the time is there.
Thanks, Onno.
Okay. Thanks very much, Graig. Our next question comes from Michael Okunewitch from the Maxim Group. Go ahead, Michael.
Hi there. Thanks for taking my question. It seems like TNF is a big part of the dual mechanism. Would you expect Toledo to work best in patients with disease phenotypes that are likely to respond to TNF therapy? Or is the dual mechanism likely to expand the population which is likely to respond?
For the great question here. Well, the Toledo profile, we focus it a slight bit on TNF, but there is a large array of pro-inflammatory cytokines we block because I have asked the same question, IL-12, IL-23. As I said, I believe that by playing at both ends, we should be capable of showing activity with more patients to start with, I hope. I think that is the question, but I know that the slides were around TNF, but you could have made slides on other cytokines. That is the beauty of this program. It is quite broad, and it really blocks that whole NF-κB program there, which is triggering a large variety of the cytokines. It is not limited to TNF. It is also decreasing IL-1β, interferon, whatever. In that sense, we should have a quite broad view on where it can play.
It's my belief that with this profile, in the end, we should be able of aiming higher on the dose response, and that will then give us a better profile. Thank you.
All right. Thank you. One more, if you don't mind. I'd just like to touch on, you have the dual mechanism, which is essentially rebalancing the immune system rather than pure suppression. Would you anticipate that you would avoid many of the side effects associated with traditional anti-inflammatories?
Yeah, that's indeed the anticipation. That's correct.
All right. Thanks very much, Michael. Our next question comes from our first question poser today. That's Brian Abrahams of RBC. Thanks for your patience, Brian. Your line is now open.
Thanks, Elizabeth, and thanks for taking my follow-up question. I think studies have shown that SIK1 may play a role in maintaining muscle health, and I think studies have also shown topical pan-SIK inhibitors may be associated with increased skin pigmentation. I guess I'm curious specifically about whether you're looking at some parameters along those lines like perhaps CK or pigmentation in the ongoing studies, and if you've seen anything of note so far. With respect to therapeutic window, I'm curious where you're expecting to dose in the ongoing proof of concept studies relative to the equivalent dose levels at which you saw the impressive activity in the animal models. Thanks.
Yeah. Thanks. I'll take those. Yes, essentially, as I mentioned, commensurate with the size of our investment, we were also not just looking to understand the biology just in terms of efficacy, but understanding the biology period with whatever effect there are in humans. You can imagine we had a large team dedicated to it, both preclinical and clinical, looking at this, and we monitor all of these elements that you mentioned. We're quite aware of the work that's being done with topical use of the SIK inhibitors. In terms of therapeutic window, the preclinical data or I'm sorry, the pharmacodynamic phase I data that Piet shared with you showed you very nicely that we do have a very good response, both on innate and adaptive immunity and changes in IL-10 and TNF-α.
With those, when we dose in the clinic, we're going to be taking a dose, at least in the signal detection, that will be there targeting both because that's actually what we believe is needed to show the better efficacy. In the dose range-finding studies, we will have a broader exploration so that we can see the relative impact of the various inhibition of the TNF-α, but also I think other cytokines as well, as well as the increase in IL-10 as well, and whether more increase is better or how do we characterize those response curves. That's going to be also very interesting data that we'll be generating from those range-finding studies.
That's really helpful. Thank you.
All right. Thanks so much to everyone who's participated. This does conclude the Q&A part of our R&D roundtable. Please reach out to me or to Sofie Van Gijsel if you still have questions and/or if you'd like to obtain some of the references mentioned during the webcast. Our next scheduled financial results call will be for the Q3 results at 8:00 A.M. Eastern, 2:00 P.M. Continental Time in Europe on the 6th of November. We'll publish our results the evening before, after U.S. market close. We thank all callers for their participation and please, all of you, stay safe and well. Thank you very much. Goodbye.